Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
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Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.6877709
Accumulation of cells in G 1 was accompanied by an attenuation of Rb protein phosphorylation associated with decreased CDK 4 and CDK 2 activities . 0.6877709^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.63756924
We further demonstrated a different mechanism for gankyrin to facilitate the phosphorylation of Rb , by binding with cyclin dependent kinase 4 ( CDK 4 ) . 0.63756924^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
CDKN2 / p16 or RB alterations occur in the majority of glioblastomas and are inversely correlated . p 16 is involved in a cell cycle regulatory cascade that includes cyclin dependent kinase 4 ( cdk 4 ) , cyclin D 1 , and pRb ( retinoblastoma ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Upon C2C12 myogenesis , the level of the cyclin dependent kinase 4 ( CDK 4 ) protein does not change , but its Rb kinase activity is down regulated markedly . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Analysis of the Rb gene and cyclin dependent kinase 4 inhibitor genes ( p16INK4 and p15INK4B ) in human ovarian carcinoma cell lines . ^^^ In the present study , we analyzed human ovarian carcinoma cell lines for abnormalities in the tumor suppressor gene Rb ( retinoblastoma ) and in cyclin dependent kinase 4 ( CDK 4 ) inhibitor genes ( p16INK4 and p15INK4B ) using molecular biology techniques . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The Rb / p16 tumor suppressive pathway is abrogated frequently in human tumors , either through inactivation of the Rb or p16INK4a / CDKN2 / MTS1 tumor suppressor proteins , or through alteration or overexpression of the cyclin D 1 or cyclin dependent kinase 4 oncoproteins . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The mammalian cell cycle is controlled by regulators of the G 1 to S transition such as tumor suppressor proteins , p 53 and retinoblastoma ( RB ) ; cyclin D 1 and cyclin dependent kinase 4 ; and inhibitor of cyclin dependent kinase , p16INK4A . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Members of the INK 4 protein family specifically inhibit cyclin dependent kinase 4 ( cdk 4 ) and cdk 6 mediated phosphorylation of the retinoblastoma susceptibility gene product ( Rb ) . p16INK4A , a prototypic INK 4 protein , has been identified as a tumor suppressor in many human cancers . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
However , phosmidosine inhibited hyperphosphorylation of retinoblastoma ( RB ) protein by RB kinases such as cyclin dependent kinase 4 and cyclin dependent kinase 2 , probably as a result of the inhibition of cyclin D 1 expression . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The correlation coefficient ( r 2 ) between doubling time ( DT ) and cyclin D 1 in the 14 cell lines that doubled within 47 . 2 h was 0 . 4856 , while the r 2 between DT and cyclin dependent kinase 4 ( CDK 4 ) and that between DT and RB among those cell lines were 0 . 3761 and 0 . 0874 , respectively . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Osteosarcomas often suffer mutations of the RB ( retinoblastoma ) gene , with resultant inactivation of the pRb protein . pRb is one component in a cell cycle control pathway that includes the p 16 ( encoded by the CDKN2A gene ) and cyclin dependent kinase 4 ( cdk 4 , encoded by the CDK 4 gene ) proteins . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
One Rb pathway alteration seen in high grade astrocytomas is amplification of cyclin dependent kinase 4 ( CDK 4 ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Several regulators of E2F transcriptional activity , including the retinoblastoma tumor suppressor ( Rb ) protein , p16Ink4a , cyclin D 1 , and cyclin dependent kinase 4 , have been shown to be targets for genetic alterations that underlie the development of human cancers . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The genes investigated have been shown previously to be altered during human glial tumour progression and include the gene for the epidermal growth factor receptor ( EGFR ) , the genes for the cell cycle regulators cyclin dependent kinase 4 ( CDK 4 ) , cyclinD 1 ( cycD 1 ) , the p 16 gene ( MTS1 / INK4 ) and the retinoblastoma gene ( RB ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
LPTs failed to upregulate cyclin dependent kinase 4 and cyclin D 3 , but Rb phosphorylation and cyclin A and B 1 upregulation were induced by CD 2 engagement . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Cyclin D 1 and its partner , cyclin dependent kinase 4 ( CDK 4 ) , are important for promoting the G 1 to S phase progression via phosphorylation of the retinoblastoma ( Rb ) protein . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The crystal structure of gankyrin , an oncoprotein found in complexes with cyclin dependent kinase 4 , a 19 S proteasomal ATPase regulator , and the tumor suppressors Rb and p 53 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Cyclin dependent kinase 4 ( Cdk 4 ) and Cdk 6 , and later Cdk 2 , in association with their specific cyclin partners , regulate the G 1 to S phase cell cycle transition of mammalian cells by phosphorylation of retinoblastoma ( Rb ) family proteins . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Using different E 7 mutant proteins , dominant negative cyclin dependent kinase 4 , and p 16 RNA interference , we demonstrate that Rb related and Rb independent mechanisms of E 7 are necessary for subversion of PML induced senescence and we identify PML as a novel target for E 7 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The serine threonine kinase cyclin dependent kinase 4 ( cdk 4 ) works in a complex with D type cyclins to phosphorylate RB , mediating the entry of cells into the cell cycle in response to external stimuli . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Cyclin D 1 or D 3 expression does not vary in the clinical course , but that alone is insufficient to promote cell cycle progression unless cyclin dependent kinase 4 ( cdk 4 ) is also elevated , in the absence of cdk 6 , to phosphorylate the retinoblastoma protein ( Rb ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Although histone H 1 kinase activity is not detected in cyclin D or PSK J 3 immunoprecipitates , cyclin D p34PSK J 3 complexes assembled in vitro stably bind and phosphorylate the retinoblastoma gene product ( pRb ) and an Rb like protein ( p 107 ) but do not interact with pRb mutants that are functionally inactive . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
TNF alpha did not affect complexes between cyclin D and Cdk 2 , Cdk 4 , and Rb proteins in MCF 7 cells . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Since most hematological malignancies except ALL are infrequently associated with p16INK4A and retinoblastoma ( Rb ) gene alteration it seems worthwhile to explore cdk 4 and cdk 6 expression to determine whether or not the disruption of the p16INK4A / Rb / cdk4 / cdk6 regulatory loop might play a role in their pathogenesis . . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The delayed G 0 > S progression in fos expressing cells was accompanied by the inappropriate levels or kinetics of expression of several cell cycle regulated genes ( cyclin D 1 , cdc 2 , cdk 2 , cdk 4 and rb ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In contrast to aberrant lack of p 16 expression in the majority of RB positive cell types , expression of apparently normal ( as shown by electrophoretic mobility and / or the ability to form protein protein complexes with cdk 4 in vivo ) p 16 was uniformly preserved in the cancer cell lines whose RB function was compromised . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
D type cyclins , in association with the cyclin dependent kinases Cdk 4 or Cdk 6 , promote progression through the G 1 phase of the cell cycle by phosphorylating the retinoblastoma protein ( RB ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The increases in Cdk 4 and cyclin D 2 expression seen in competent T cells were functionally significant since Cdk 4 immunoprecipitates from these cells phosphorylated recombinant RB protein in vitro . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
D type cyclins , in association with the cyclin dependent kinases Cdk 4 or Cdk 6 , regulate events in the G 1 phase of the cell cycle and may contribute to the phosphorylation of the retinoblastoma gene product ( Rb ) . ^^^ However , in cells in which the function of Rb has been compromised , either by naturally arising mutations or through binding to proteins encoded by DNA tumour viruses , Cdk 4 and Cdk 6 are not associated with D cyclins . ^^^ Since Rb negative cells express high levels of p 16 , we suggest that in these cells p 16 competes with D cyclins for binding to Cdk 4 and Cdk 6 and prevents formation of active complexes . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Constitutive expression of Cdk 4 , but not cyclin D 2 or D 3 , increased cyclin D 2 associated Rb kinase activity and this activity could no longer be inhibited by TGF beta 1 . ^^^ Also , in vivo phosphorylation of Rb was inhibited by TGF beta 1 in wild type but not in Cdk 4 lines . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Cell cycle dependent phosphorylation of the RB tumor suppressor protein is mediated by a family of G 1 cyclin dependent kinases ( cdks ) and cyclins including the activated cdk 4 : cyclin D complex . ^^^ The identification of a cdk 4 inhibitor , p16INK4 , as a target for mutations in cultured tumor lines and primary tumors suggested that RB activity may be affected in these cells . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Coexpression of the three D type cyclins with the cyclin dependent kinase ( cdk 4 ) in insect cells generated Rb kinase activity . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Cdk 4 ( cyclin dependent kinase ) , a major catalytic subunit of the mammalian D type G 1 cyclins , can phosphorylate Rb in vitro , and at least one D type cyclin , D 2 , directs the phosphorylation of Rb in vivo . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Furthermore , the retinoblastoma protein ( Rb ) , a substrate of cdk 4 and cdk 2 whose phosphorylation is necessary for cell cycle progression , remains underphosphorylated in PGA 2 treated serum stimulated cells . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Cyclin D 1 binds to Cdk 4 and forms a complex , then binds to and phosphorylates Rb protein thus triggering cells to progress from G0 / G1 to S and thus drives cellular proliferation . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Only p 36 ( D ( 1 ) ) p 34 ( cdk 4 ) complexes are activated by E ( 2 ) , as detected in cell extracts by immunoprecipitation with anti D ( 1 ) antibodies followed by assessment of phosphotransferase activity toward the retinoblastoma ( Rb ) gene product and by analysis of p 105 ( Rb ) phosphorylation in vivo . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The kinase activity of the immunoprecipitated Cdk 4 was determined using recombinant Rb as substrate . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Cdk 4 associated Rb kinase activity was evident in MCF 7 cells by 6 h after estradiol exposure and was inhibited by antiestrogen . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
A series of 195 human gliomas were studied as to the status of their CDKN2A , CDK 4 and RB 1 genes . ^^^ In the glioblastomas with no alterations of CDKN2A , CDK 4 or RB 1 , several other genes ( CCND 1 , CCND 2 , CCND 3 , CDK 6 , E2F , CDK 7 , MYC and MYCN ) whose products take part in cell cycle regulation were examined . ^^^ Thus some aberration of the CDKN2A , CDK 4 and RB 1 genes appears to be almost obligatory in glioblastomas . . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
These results suggest that homozygous CDKN2 / p16 deletions in high grade astrocytomas may have a more deleterious effect on cell cycle control than the other aberrations in the p 16 cdk4 cyclin D 1 pRb pathway , and may provide one explanation for why homozygous CDKN2 / p16 deletions are more common genetic events in high grade astrocytomas than RB mutations or CDK 4 amplification . . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The cyclin D dependent kinases CDK 4 and CDK 6 trigger phosphorylation of the retinoblastoma protein ( RB ) late in G 1 phase , helping to cancel its growth suppressive function and thereby facilitating S phase entry . ^^^ Although specific inhibition of cyclin D dependent kinase activity in vivo can prevent cells from entering S phase , it does not affect S phase entry in cells lacking functional RB , implying that RB may be the only substrate of CDK 4 and CDK 6 whose phosphorylation is necessary for G 1 exit . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
An obvious focus is the so called restriction point in late G 1 , and current evidence suggests that this is in part determined by the phosphorylation of the retinoblastoma protein ( Rb ) by the cyclin D dependent kinases , CDK 4 and CDK 6 . ^^^ Downstream targets of Rb , such as the E2F1 transcription factor , can promote cell cycle progression , whereas inhibitors of CDK 4 and CDK 6 , such as p16CDKN2a , can block G 1 progression . ^^^ Many human tumours have been shown to have chromosomal abnormalities that directly affect components of this pathway , resulting in either the functional inactivation of p 16 or Rb or the excessive activity of cyclin D 1 or CDK 4 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The PCR products for cyclins D 1 , D 3 , and A , as well as cdk 4 , p 21 , and Rb , displayed similar levels in meiotically incompetent and competent oocytes , as well as in metaphase 2 arrested eggs . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
To determine a possible mechanism by which senescent human fibroblasts maintain a hypophosphorylated Rb , we examined the expression levels and interaction of the Rb kinases , CDK 4 and CDK 6 , and the cyclin dependent kinase inhibitors p 21 and p 16 in senescent HDFs . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
These proteins bind to , and regulate cyclin dependent kinase ( CDK ) , such as CDK 4 , responsible for phosphorylation of retinoblastoma ( RB ) and dissociation of RB E2F1 inhibitory complexes , thereby allowing progression through the cell cycle . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The down modulating effects of the inhibitors on the expression of the following cell cycle regulators have been examined : c myc , cyclin D 1 and D 2 , cdk 4 , Rb phosphorylation , E2F binding activity , ribonucleotide reductase subunits , and PCNA . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
On the other hand , there was no significant difference in expression of proteins such as Rb , p 16 , cdk 4 , cdk 6 , cyclin A and cyclin D 1 between the normal and immortalized human fibroblasts . . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
These studies show that Rb interaction with E2F1 is regulated by cdk 4 and cyclin D 1 within p 210 BCR ABL transformed leukemia cells in early G 1 phase of the cell cycle . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
GR activation in U2OS cells represses expression of the cyclin dependent kinases ( CDKs ) CDK 4 and CDK 6 as well as their regulatory partner , cyclin D 3 , leading to hypophosphorylation of the retinoblastoma protein ( Rb ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Anaplastic astrocytomas further display release of a critical cell cycle brake that involves the CDKN2 / p16 , RB and CDK 4 genes . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Analysis of expression of genes regulating Rb phosphorylation revealed that activin A suppressed cyclin D 2 , the sole D type cyclin gene expressed in the hybridoma cells , and activated p21CIP1 / WAF1 but had no effect on expression of cyclin dependent kinases ( CDK 2 , CDK 4 , CDK 6 ) and other CDK inhibitors ( p27KIP1 , p16INK4a , p15INK4b ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Immunoblots utilizing an antibody against the 110 kDa retinoblastoma protein ( Rb ) , a downstream phosphorylation target of the cyclin D1 / cyclin dependent kinase 4 ( cdk 4 ) complex , showed reduced electrophoretic mobility of this protein as early as 8 h after PDGF treatment , suggesting phosphorylation of Rb by the cyclin D1 / cdk4 dimer in vivo . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
FISH analysis further revealed tetraploidy / aneuploidy in 14 ( 47 % ) , RB deletion in 11 ( 37 % ) and CDK 4 amplification in 1 ( 3 . 3 % ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In the present study , primary and secondary glioblastomas were analyzed for p 16 deletions and CDK 4 amplification by differential PCR and for loss of expression of the retinoblastoma ( RB ) gene by immunohistochemistry . ^^^ Except for one case , alterations in the structure or expression of p 16 , CDK 4 and RB were mutually exclusive . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Involvement of p 21 ( WAF1 / Cip1 ) , CDK 4 and Rb in activin A mediated signaling leading to hepatoma cell growth inhibition . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Mutations in Rb , cyclin D 1 , its catalytic subunit Cdk 4 , and the CDKI p16Ink4a , which alter the protein or its level of expression , are all strongly implicated in cancer . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
A mathematical model integrating the roles of cyclin D , cdk 4 , cyclin E , cdk 2 , E2F and RB in control of the G 1 phase of the cell cycle is described . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Expression of CDK 4 and 6 along with several cyclins also did not coincide with the appearance of phosphorylated RB in the apoptotic process . . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
We investigated the status and expression of p 16 , p 15 , CCND 1 , CDK 4 and RB genes in the Ewing family of tumors . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
These alterations lead to changes in the expression of several genes ; protein 53 ( p 53 ) , retinoblastoma ( RB ) , interferon ( INF ) alpha / beta , cyclic AMP dependent kinase number 2 ( CDKN 2 ) , mutated in multiple advanced cancers 1 ( MMAC 1 ) , deleted in colon carcinoma ( DCC ) , epidermal growth factor receptor ( EGFR ) , platelet derived growth factor ( PDGF ) , platelet derived growth factor receptor ( PDGFR ) , MDM 2 , GL 1 , CDK 4 and SAS during the genesis and progression of human gliomas . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
These results suggest that the expression of cyclin D 1 , CDK 4 , Rb and p 27 is associated with the p 16 gene status in esophageal carcinoma cell lines . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
We also reviewed associated studies on CDK 4 and RB 1 involvement in melanoma , and examined the role of p16 / CDKN2A in other inherited cancers . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Furthermore , two cyclin dependent kinases , cdk 2 and cdk 4 , which are normally involved in the phosphorylation of Rb , were shown to have decreased activity . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
TSH and EGF+serum also induced a previously undescribed nuclear translocation of cdk 4 , the assembly of precipitable cyclin D 3 cdk4 complexes , and the Rb kinase activity of these complexes . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Twenty primary central nervous system lymphomas ( PCNSL ) from immunocompetent patients ( nineteen B cell lymphomas and one T cell lymphoma ) were investigated for genetic alterations and / or expression of the genes BCL 2 , CCND 1 , CDK 4 , CDKN1A , CDKN2A , MDM 2 , MYC , RB 1 , REL , and TP 53 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In the majority of cases , CDK 4 overexpression accompanied elevated p 16 and / or RB levels . ^^^ Our results suggest that : ( a ) alteration of the p 16 gene is infrequent in primary soft tissue sarcoma ; ( b ) Cdk 4 may act as an oncogene in soft tissue sarcoma ; and ( c ) elevated p 16 and RB levels might be the result of compensatory up regulation of these proteins to counteract CDK 4 overexpression in these tumors . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Nearly all human gliomas exhibit alterations in one of three genetic loci governing G 1 arrest : INK4a ARF , CDK 4 , or RB . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Moreover , the overexpression of Rb or CDK 4 reduced the level of TAF ( 2 ) 250 cyclin D 1 complex . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The vast majority of glioblastomas have CDKN2A , CDK 4 , or RB gene alterations that perturb the p 16 cdk4 pRb cell cycle regulatory cascade . ^^^ Homozygous deletion of the CDKN2A gene was detected in 12 of 25 ( 48 % ) cases , CDK 4 amplification in 4 of 25 ( 16 % ) tumors , and loss of heterozygosity at the RB gene in 8 of 22 ( 36 % ) informative cases . ^^^ Significantly , all of these had either CDK 4 amplification or RB LOH , suggesting that p 16 immunopositivity only occurs in those tumors with alterations of another component in the pathway . ^^^ From a practical point of view , although p 16 immunonegativity does not necessarily indicate CDKN2A deletion , diffuse positive p 16 immunostaining strongly suggests either CDK 4 amplification or RB loss and excludes CDKN2A deletion . . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
We have determined the minimal portion of the retinoblastoma protein ( Rb ) that can serve as an efficient substrate for in vitro phosphorylation by cdk 4 kinase D 1 cyclin . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In the search for new risk factors at the molecular and cellular levels , clinical data [ lymph node involvement ( LN ) and stage ] were used and 104 squamous cell lung carcinomas were analyzed by immuno histochemistry for expression of cyclin D 1 , cyclin A , cdk 2 , cdk 4 , RB , and E2F1 . ^^^ The results of the univariate analysis of all 8 factors showed that cyclin A and cdk 2 gave the best prognostic information , while no prognostic value could be found associated with cyclin D 1 , cdk 4 , RB and E2F1 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
To test this hypothesis , a recently developed quantitative reverse transcriptase polymerase chain reaction method was used to assess simultaneously expression of 15 genes mechanistically associated with cell cycle control ( c myc , E2F 1 , p 21 , rb , PCNA , cyclin D 2 , cyclin D 3 , cyclin E , cdc 2 , CDK 2 , CDK 4 , mad , max p 21 , max p 22 , and p 53 ) in normal cell cultures from five individuals and in nine different malignant BEC lines . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The expression of cyclin D 1 , cdk 4 , p16INK4a , and Rb protein was examined by immunohistochemistry in 4 ( methylnitrosamino ) 1 ( 3 pyridyl ) 1 butanone ( NNK ) induced mouse lung tumors . ^^^ These results suggest that alterations in the cell cycle proteins , cyclin D 1 , cdk 4 , p16INK4a , and Rb , may play a role in the acquisition of autonomous growth by adenomas . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
To address this issue further , we investigated five typical and three aggressive ( blastoid ) MCL for alterations in the cell cycle regulating genes p 15 , p 16 , CDK 4 , Rb and p 53 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In total , 11 / 12 MPNSTs showed DNA changes in one or more of the genes CDKN2A , CDKN2B , RB 1 , CDK 4 , MDM 2 , and CCND 2 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Survivin also interacts with the cell cycle regulator Cdk 4 , leading to Cdk2 / Cyclin E activation and Rb phosphorylation . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Overexpression of cdk 2 and cdk 4 but not a dominant negative cdk 2 rescued Rb mediated downregulation of telomerase activity . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The Cdk 4 substrate , retinoblastoma ( Rb ) protein , is also induced in apoptotic cells . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Amplification of the CDK 4 gene in sarcomas : tumor specificity and relationship with the RB gene mutation . ^^^ We also investigated the relationship of CDK 4 amplification with retinoblastoma ( RB ) gene mutations in osteosarcomas , for which we have already performed the mutation analyses in detail . ^^^ Interestingly , contrary to the prevailing theory that CDK 4 amplification is an alternative mechanism for RB gene mutation , we found that three of four cases with amplification of the CDK 4 gene showed loss of expression of the RB protein , one of which was proved to have an gross DNA alteration in the RB locus . ^^^ This redundancy of mutations may indicate that the amplification of CDK 4 may have some roles other than the inactivation of the RB protein in the development of osteosarcomas . . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Initial studies showed that treatment of MCF 7 cells with 10 nM E 2 significantly increased cyclin D 1 ( protein and mRNA ) , cdk 2 and cdk 4 dependent kinase activities , and hyperphosphorylation of retinoblastoma ( RB ) protein . ^^^ For example , TCDD significantly inhibited E 2 induced hyperphosphorylation of RB , cyclin D 1 protein , and cdk 2 , cdk 4 , and cdk 7 dependent kinase activities . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
To investigate further the observed biological effects , cyclin D 1 and cdk 4 expression and the level of phosphorylation of the retinoblastoma protein Rb were assessed . ^^^ Cyclin D 1 and cdk 4 expression and Rb phosphorylation were significantly reduced , by 40 75 % , after 24 hr of treatment with RA or 4HPR ; these decreases were either transient , e . g . , only at 24 hr for cdk 4 , or sustained for 72 hr . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Abnormalities in the p16INK4A , CDK 4 , and Rb genes , which regulate transition through G 1 phase of the cell cycle , have been implicated in the progression of diverse types of cancer . ^^^ To evaluate the involvement of p16INK4A , CDK 4 , and Rb in the tumorigenesis of meningiomas , the status of these genes or gene products were examined . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Defining the substrate specificity of cdk 4 kinase cyclin D 1 complex . cdk 4 kinase cyclin D 1 complex ( cdk4 / D1 ) does not phosphorylate all of the sites within retinoblastoma protein ( Rb ) equally . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In addition , RA had no effect on the levels of Bcl XL ; Bcl XS ; cyclins A , B , D 1 , D 3 , or E ; or Rb 1 expression but markedly down modulated Cdk 2 kinase activity and reduced Cdk 4 expression . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
A cdk 2 inhibitor , Olomoucine , as well as a dominant negative cdk 2 construct prevented HLA class 1 mediated inactivation of Rb ; in contrast , dominant negative cdk 4 and cdk 6 constructs had no effect . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Cyclin D Cdk 4 complexes have a demonstrated role in G 1 phase , regulating the function of the retinoblastoma susceptibility gene product ( Rb ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In addition , we made an immunohistochemical investigation of cyclin D 1 and cdk 4 , which are involved in the Rb pathway . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Aberrant expression of the cell cycle associated proteins TP 53 , MDM 2 , p 21 , p 27 , cdk 4 , cyclin D 1 , RB , and EGFR in cervical carcinomas . ^^^ OBJECTIVE : The aims of this study were to study aberrant expression and coexpression of the cell cycle associated proteins TP 53 , p 21 , p 27 , cyclin D 1 , cdk 4 , RB , EGFR , and MDM 2 in cervical carcinomas , to correlate protein alterations with histopathological and clinical parameters , and to evaluate whether these alterations provide prognostic information . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
To identify the possible genes included in the abnormal chromosome regions , selected cases were analyzed for P 53 , P 16 ( INK4a ) , RB , C MYC , N MYC , BCL 2 , BCL 6 , CDK 4 , and BMI 1 gene alterations . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
These include mutation and / or deletion of the retinoblastoma ( RB 1 ) gene , homozygous deletion of the CDKN2A and CDKN2B genes , as well as amplification and overexpression of the CDK 4 and CDK 6 genes . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Cellular signal transduction cascades triggered by mitogenic or antiproliferative cues eventually converge on a biochemical mechanism centered around the retinoblastoma tumor suppressor ( pRb ) , the so called RB pathway that governs G 1 phase progression and guards the commitment to enter S phase . pRb , together with its immediate upstream regulators , the D type cyclins , their partner cyclin dependent kinases Cdk 4 and Cdk 6 , and the Cdk inhibitors , form a functional unit that is involved in major decisions about cellular fate , and whose components , including the proto oncogenic cyclin D dependent kinases , are commonly deregulated in many types of cancer . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Cdk 4 and Cdk 6 immune complexes recovered from B cells following BCR Fc gamma R co cross linking are devoid of coprecipitated D type cyclins , indicating that inhibition of their Rb protein kinase activities is due in part to the absence of bound D type cyclin . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
MEN 1 gene , although found in some sporadic tumors , is more likely associated with familial adenoma . p 53 , Ras , Rb , nm 23 and c myc genes play some role in the promotion of tumors especially toward their aggressive variant . p 53 gene , which is found in up to 60 % of ACTH producing adenomas , through action of p 21 inhibits progression of cell cycle from G 1 to S phase , by inhibiting the action of cyclin D 3 on cdk 4 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
This cell cycle perturbation by CDK 4 disruption was associated with increased binding of p 27 to cyclin E / CDK2 and diminished activation of CDK 2 accompanied by impaired Rb phosphorylation . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
PATIENTS AND METHODS : The expression patterns and their possible prognostic relevance of the cell cycle regulatory proteins p 53 , p 21 ( WAF / CIP1 ) , Rb , p 16 ( INK4A ) , CDK 4 and Cyclin D 1 , MIB 1 ( Ki 67 ) and BCL 2 were analysed in pretreatment tumor biopsies from 43 patients with advanced carcinomas of the oropharynx ( n = 26 ) , hypopharynx ( n = 10 ) and larynx ( n = 7 ) by applying immunohistochemistry to paraffin sections of tumor specimens . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The positive percentage of cyclin D 1 , CDK 4 , p 16 and Rb was 66 . 7 % , 53 . 3 % , 33 . 3 % , and 36 . 7 % , respectively . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Detection of p 16 , RB , CDK 4 , and p 53 gene deletion and amplification by fluorescence in situ hybridization in 96 gliomas . ^^^ Alternatively , since the p 16 , retinoblastoma ( RB ) , and CDK 4 genes have been implicated in malignant progression , detection of losses or amplifications of these genes in gliomas could be diagnostically , prognostically , and therapeutically important . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In addition to the INK4a locus , other genes involved in melanoma development are discussed here , in particular those genes that participate in the same functional pathway , such as CDK 4 and Rb , and p 53 , which is regulated by the alternative product of INK4a . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Both p 16 and p 15 , encoded by genes located on chromosome 9p21 , are inhibitors of cyclin dependent kinases 4 / 6 ( CDK4 / 6 ) and upstream regulators of RB function , and set up the RB / p16 tumor suppressive pathway , which is abrogated frequently in human neoplasms , either through inactivation of the RB or p 16 tumor suppressor protein , or alteration of the cyclin D 1 or CDK 4 oncoproteins . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Loss of p16INK4a expression would disrupt the retinoblastoma ( Rb ) / p16INK4a / cyclin D dependent kinase ( CDK 4 ) pathway , whereas loss of p14ARF expression would inactivate both the Rb and p53 / MDM2 / p14ARF pathways through MDM 2 , which can complex with either Rb or p 53 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The overall incidence of alterations in the Rb pathway ( p 16 deletion , CDK 4 amplification , or loss of pRb immunoreactivity ) was 53 % , and these changes were mutually exclusive . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
We have previously reported that approximately two thirds of glioblastomas ( GBs ) had abnormalities of G 1 S transition control either by mutation / homozygous deletion of RB 1 or CDKN2A p16INK4A ) , or amplification of CDK 4 ( K . ^^^ Sixty seven percent of GBs ( 91 / 136 ) and 21 % of AAs ( 8 / 39 ) had abnormalities of the G 1 S control system either by mutation / homozygous deletion of RB 1 , CDKN2A or CDKN2B , or amplification of CDK 4 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Furthermore , ( 1 ) the arrest of G ( 1 ) S transition exerted by PC 3 was completely rescued by coexpression of cyclin D 1 but not by that of cyclin A or E ; ( 2 ) expression of PC 3 caused a significant down regulation of cyclin D 1 protein levels , also in Rb defective cells , accompanied by inhibition of CDK 4 activity in vivo ; and ( 3 ) the removal from the PC 3 molecule of residues 50 to 68 , a conserved domain of the PC3 / BTG / Tob gene family , which we term GR , led to a loss of the inhibition of proliferation as well as of the down regulation of cyclin D 1 levels . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The most frequent genetic alterations include inactivation of the p 53 , p 16 , Rb and PTEN genes , and overexpression of the CDK 4 , EGFR and VEGF genes . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
This affinity peptide tagged protein ( GST Rb 152 StrepTag ) , which contains the two known phosphorylation sites of Rb , specifically phosphorylated by Cdk 4 in vivo , was used as a substrate in the current in vitro kinase assay . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
D cyclin cdk activity is required for Rb phosphorylation in 5 Jun transformed cells , since ectopic expression of the cdk 4 and cdk 6 specific inhibitor p 16 ( INK4A ) inhibits both DNA synthesis and cell proliferation . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Cpd 5 enhanced tyrosine phosphorylation of both potent regulators of G 1 transition , ie . , Cdk 2 and Cdk 4 , and decreased the phosphorylation of Rb , an endogenous substrate for Cdk 4 kinase . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
This resistance is associated with low expression of p15ink4b and p16ink4a , constitutive Rb phosphorylation and high levels of cdk 4 and cdk 2 kinase activity . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
To investigate whether alteration of other components in pRb pathway is an alternative mechanism underlying the development of these chemically induced lymphomas , we have examined the genetic status of Rb 1 , Ccnd 1 and Cdk 4 genes that encode retinoblastoma protein , cyclin D 1 and cyclin dependence kinase 4 , respectively . ^^^ Gross alterations of the Rb 1 , Ccnd 1 , and Cdk 4 genes were not detected by Southern analysis in any of the tumors examined . ^^^ These results indicate that the mechanisms underlying the development of 2 ' , 3 ' dideoxycytidine and 1 , 3 butadiene induced lymphomas involve inactivation of p16 / p15 cyclin dependent kinase inhibitors but not genomic alterations of the Rb 1 , Ccnd 1 and Cdk 4 genes . . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Ectopic expression of PSM RB in SAOS 2 cells resulted in a decrease in both Cyclin A and Cdk 2 protein levels without affecting Cyclin E or Cdk 4 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In the present study , we analysed 34 de novo diffuse large B cell lymphoma ( DLCL ) from a population based lymphoma registry for alterations of the RB 1 pathway at the genetic ( RB 1 and CDK 4 ) and protein ( pRb , cyclin D 1 , cyclin D 3 , CDK 4 , and E2F 1 ) level . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Furthermore , cyclin dependent kinases 2 and 4 ( Cdk 2 and Cdk 4 ) , which are involved in the phosphorylation of Rb , were also decreased . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In this paper , the presence of SV 40 like sequences was investigated in 54 Japanese osteosarcomas in which mutations of the retinoblastoma ( Rb ) , p 53 , MDM 2 , and CDK 4 genes had been already analysed . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In the same cells , a decrease in the phosphorylated form of Rb protein and an increase in the p 130 protein were observed without changes in the protein level of cell cycle dependent kinase 2 ( Cdk 2 ) , Cdk 4 , and Cdk 6 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Accumulation of p 21 ( CIP1 / WAF1 ) resulted in increased binding of p 21 ( CIP1 / WAF1 ) to CDK 4 and concomitantly caused a profound decrease in the in vitro retinoblastoma protein ( Rb ) kinase activity of CDK 4 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
TP 53 alterations in relation to the cell cycle associated proteins p 21 , cyclin D 1 , CDK 4 , RB , MDM 2 , and EGFR in cancers of the uterine corpus . ^^^ In the present study , TP 53 alterations have been analysed and compared with the expression of the proteins p 21 , cyclin D 1 , cdk 4 , RB , EGFR , and MDM 2 in 53 cancers of the uterine corpus . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Mitogen dependent , cyclin D dependent kinases ( cdk 4 and cdk 6 ) phosphorylate the retinoblastoma ( Rb ) tumor suppressor protein , helping to cancel its growth inhibitory effects and enabling E2F transcription factors to activate genes required for entry into the DNA synthetic phase ( S ) of the cell division cycle . ^^^ Lesions in the p 16 cyclin D CDK 4 Rb and ARF Mdm 2 p 53 pathways occur so frequently in cancer , regardless of patient age or tumor type , that they appear to be part of the life history of most , if not all , cancer cells . . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Fifty three neuroendocrine lung tumors ( 24 carcinoids , one atypical carcinoid , five large cell neuroendocrine carcinomas , and 23 small cell lung carcinomas ) were investigated for immunocytochemical expression of several gene products , i . e . , p 53 , Rb , bcl 2 , c kit , mdm 2 , cdk 4 , p 21 proteins , and proliferation index as assessed by MIB 1 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Overexpression of wild type waf 1 in melanoma cells reduced growth of subconfluent cells , decreased Cdk 4 activity with a concomitant increase in hypophosphorylated Rb , and promoted cell death by apoptosis . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Activity of CDK 4 or 6 , measured by phosphorylation of an Rb fragment , remained constant during the response period ; however , activity of CDK 2 ( phosphorylation of histone H 1 ) decreased . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Re expression of myc activates the cell cycle without inducing apoptosis . myc triggers the expression of cyclin D 2 , cyclin E and Cdk 4 , followed by the activation of cyclin E associated kinase and hyper phosphorylation of Rb . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The p16ink4a cyclin D1 / cyclin dependent kinase 4 ( Cdk 4 ) retinoblastoma ( Rb ) pathway has emerged as a critical target in oncogenesis . ^^^ Expression of p16ink4a , cyclin D 1 , Cdk 4 , and Rb in relation to that of proliferating cell nuclear antigen was characterized in esophagi by immunohistochemistry at 0 , 24 , and 48 h , and 1 , 3 , 7 , 10 , and 14 weeks after NMBA treatment . ^^^ At the same time , overexpression of cyclin D 1 , Cdk 4 , and Rb was found in the corresponding lesion in adjacent esophageal sections . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Here , we show that DROSOPHILA : Cdk 4 interacts with Cyclin D and the Rb homolog RBF as expected , but is not absolutely essential . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The re expressed p16INK4A was functional , because it bound to and inhibited CDK 4 kinase activity , and increased the concentrations of the hypophosphorylated form of retinoblastoma protein ( pRB ) in cells with a wild type RB gene . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
RB , CDK 4 , MDM 2 , c myc , c fos , and p 53 gene expression , which are the major genes involved in osteosarcoma susceptibility , were studied . ^^^ Our results revealed an inactive form of p 53 sporadically seen in the samples , a total loss of Rb protein expression , an increased expression of Cdk 4 , MDM 2 , c fos , and c myc proteins which literature currently reports being the principal alterations found in osteosarcoma . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Furthermore , VES reduces cdk 4 kinase activity , Rb phosphorylation , and cyclin E mRNA expression . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Retinal cellularity was rescued in the cyclin D 1 null mouse by loss of p 27 with only a partial restoration of phosphorylation of retinoblastoma protein ( Rb ) and Cdk 4 activity but with a dramatic elevation of Cdk 2 activity . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Polymerase chain reaction ( PCR ) was used to detect loss of heterozygosity at the APC , RB , and MCC gene loci , while differential PCR was carried out to detect amplification of the CDK 4 gene . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
RESULTS : The authors demonstrate that p 53 , p 16 , retinoblastoma ( RB ) , epidermal growth factor receptor ( EGFR ) , cyclin dependent kinase 4 ( CDK 4 ) , platelet derived growth factor A ( PDGF A ) and PDGF receptor alpha ( PDGF Ralpha ) protein expression profiles are not altered in NF 1 associated pilocytic astrocytomas . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Expression of the RB protein , allelic imbalance of the RB gene and amplification of the CDK 4 gene in metaplasias , dysplasias and carcinomas in Barrett ' s oesophagus . ^^^ In the present study , the role of allelic loss at the retinoblastoma gene ( RB ) , expression of the retinoblastoma protein ( pRb ) and amplification at the CDK 4 gene in the metaplasia dysplasia carcinoma sequence in Barrett ' s oesophagus ( BO ) was investigated . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Rb phosphorylation is mediated by cyclin dependent kinases ( CDKs ) , whose activity is enhanced by cyclins and inhibited by CDK inhibitors . p 16 ( INK4A ) is a member of a family of inhibitors specific for CDK 4 and CDK 6 . p 16 ( INK4A ) is deleted and inactivated in a wide variety of human malignancies , including familial melanomas and pancreatic carcinoma syndromes , indicating that it is an authentic human tumor suppressor . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Introduction of Tax into resting Kit 225 cells induced activation of the G1 / S transition regulation cascade consisting of activation of cyclin dependent kinase 2 ( CDK 2 ) and CDK 4 , phosphorylation of the Rb family proteins and an increase in free E2F . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In Ewing cell lines , cyclin D 1 , CDK 4 , Rb , p27KIP1 and c Myc were consistently highly expressed whereas p57KIP2 , p15INK4B and p14ARF demonstrated undetectable or low expression levels . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
METHODS : We performed Western blot analysis of five cell cycle stimulating ( cyclins D 1 , E , B 1 , cdk 2 , cdk 4 ) and three cell cycle inhibiting ( p 16 ( INK4a ) , p 21 ( WAF 1 ) , Rb ) proteins in 41 endometrial carcinoma specimens . ^^^ Cyclin B 1 expression correlated with cyclin E , cdk 2 , cdk 4 , p 21 , Rb , and Ki 67 , and cyclin E expression with cyclin D 1 and Rb . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Expression levels of the AP 1 factors were correlated with clinico pathologic tumor parameters , steroid receptor status , Ki 67 expression and the expression levels of eight cell cycle regulatory proteins ( cyclin D 1 , cyclin E , cyclin B 1 , cdk 2 , cdk 4 , p 16 , p 21 , and Rb ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Gankyrin contains six ankyrin repeats and interacts with Rb , Cdk 4 , and the S 6 ATPase of the 26 S proteasome . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In addition , senescence is associated with increased binding of the cyclin dependent kinase inhibitor ( CDK 1 ) p 16 ( INK4a ) to CDK 4 , down regulation of cyclin E protein levels ( and consequent loss of cyclin E / CDK2 activity ) , underphosphorylation of the retinoblastoma protein RB and subsequent increased levels of E2F4 RB repressive complexes . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Inactivation of lin 35 Rb , the single Rb related gene in C . elegans , substantially reduced the DNA replication and cell division defects in cyd 1 and cdk 4 mutant animals . ^^^ These results demonstrate that lin 35 Rb is an important negative regulator of G1 / S progression and probably a downstream target for cyd 1 and cdk 4 . ^^^ However , as the suppression by lin 35 Rb is not complete , cyd 1 and cdk 4 probably have additional targets . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
METHODS : Expression of G 1 stimulatory ( cyclins D 1 and E , cdk 4 , Ki 67 ) and inhibitory ( p 16 , Rb , p 27 , p 14 ) genes was analyzed using Western blots in 84 primary ovarian cancers and seven cell lines of known p 53 mutation status . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Cdk 4 ( R24C / R24C ) mouse embryo fibroblasts ( MEFs ) displayed increased Cdk 4 kinase activity resulting in hyperphosphorylation of all three members of the Rb family , pRb , p 107 , and p 130 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In addition , the dephosphorylated form of Rb protein increased because of the down regulation of CDK 4 and CDK 2 activities by ATRA . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Moreover , immune complexes consisting of cyclin D 2 and cdk 4 or cyclin D 3 and cdk 4 were both functional and phosphorylated the RB protein in vitro . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
We found that the mRNA expression of the cell cycle kinase ( CDK ) inhibitor inhibitor kinase ( INK ) p 18 ( INK 4 ) , a specific inhibitor of CDK 4 , 6 , which controls the activation of the retinoblastoma ( Rb ) tumor suppressor protein phosphorylation , was decreased in the brain of adult hCOX 2 homozygous transgenics . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
We describe an in vitro model of hypertrophy in C2C12 skeletal myoblasts and demonstrate that induction of hypertrophy involves transient activation of Cdk 4 , subsequent phosphorylation of Rb , and release of HDAC 1 from the Rb inhibitory complex . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
To elucidate the biochemical processes involved in the pathogenesis of B CLL and MCL , we analyzed the expression level of a set of genes that play central roles in apoptotic or cell proliferation pathways and of candidate genes from frequently altered genomic regions , namely ATM , BAX , BCL 2 , CCND 1 , CCND 3 , CDK 2 , CDK 4 , CDKN1A , CDKN1B , E2F1 , ETV 5 , MYC , RB 1 , SELL , TFDP 2 , TNFSF 10 , and TP 53 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Recently , we demonstrated that lin 35 Rb also acts as a negative regulator of G ( 1 ) progression and likely is the major target of cyd 1 Cyclin D and cdk 4 CDK4 / 6 . ^^^ Inactivation of lin 35 Rb , efl 1 , or lin 36 allowed S phase entry in the absence of cyd 1 / cdk 4 and increased ectopic cell division when combined with cki 1 Cip / Kip RNAi . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
To avoid the confounding pleiotropic effects of HPVE 7 frequently used in such studies , here we have employed retroviral vectors over expressing CDK 4 or CDK 6 as a more representative model of naturally occurring mutations targeting the Rb pathway . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
JTE 522 inhibited the expressions of COX 2 mRNA , phosphorylated Rb , and CDK 4 proteins , while increased the levels of p 53 , p 21 , cyclin D 1 proteins , and the activity of caspase 3 in RL 95 2 cells . ^^^ CONCLUSION : JTE 522 inhibits cell proliferation and induces apoptosis in RL 95 2 cells , which may be associated with the activation of caspase 3 like proteases , down regulation of the expression of COX 2 mRNA , phosphorylated Rb , and CDK 4 proteins , and up regulation of the expressions of p 53 , p 21 , and cyclin D 1 proteins . . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Furthermore , the activities of CDK 2 and CDK 4 associated kinases were reduced in association with Rb hypophosphorylation in monensin treated CA 46 cells . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
FISH analysis was performed on the oncogene cyclin D 1 and IHC analysis on the proteins cyclin D 1 , p 53 , p 16 , cdk 4 , bcl 2 , mdm 2 and rb . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
D type cyclins bind to and activate the cyclin dependent kinases Cdk 4 and Cdk 6 , which in turn phosphorylate their downstream target , the retinoblastoma protein Rb . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Furthermore , the activities of CDK 2 , CDK 4 and CDK 6 associated kinase were reduced in association with hypophosphorylation of Rb protein . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The INK 4 family of cyclin dependent kinase ( CDK ) inhibitors negatively regulates cyclin D dependent CDK 4 and CDK 6 and thereby retains the growth suppressive function of Rb family proteins . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Inhibition of Cdk 4 activity enhances translation of p27kip1 in quiescent Rb negative cells . ^^^ We show in this work that the inhibition of Cdk 4 ( 6 ) in Rb ( / ) 3T3 cells enhances the accumulation of the p 27 ( kip 1 ) cyclin dependent kinase inhibitor when these cells are induced into quiescence . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Intact Cpd 5 treated cells had decreased cellular Cdc25A activity and increased tyrosine phosphorylation of Cdk 4 , resulting in decreased phosphorylation of retinoblastoma ( Rb ) . ^^^ Loss of Cdk 4 activity was confirmed using Cdk 4 immunoprecipitates from either Cpd 5 treated or untreated cells and measuring its kinase activity using GST Rb as target . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The increase of Cdk 4 activity in SOD 1 ( G37R ) mice was associated with an increase in nuclear Cdk 4 , cyclin D 1 , its coactivator , and with the abnormal phosphorylation of the retinoblastoma ( Rb ) protein at Cdk phosphorylation sites . ^^^ Interestingly , phospho Rb was immunoprecipitated with anti Cdk 4 but not with anti Cdk 5 antibodies , suggesting a key role for Cdk 4 in the phosphorylation of Rb . ^^^ Remarkably , the overexpression of a transgene coding for human neurofilament H , a phosphorylation sink for deregulated Cdk 5 activity by p 25 , resulted in a reduction in levels of nuclear Cdk 4 and Rb phosphorylation . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Quantitative reverse transcription polymerase chain reaction verified mRNA changes in this group , which included gadd45a , c myc , cyclin D 1 and cdk 4 , pcna , cyclin G , Rb , and E2F5 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Furthermore , the activities of CDK 2 , CDK 4 and CDK 6 associated kinase were reduced and the lack of the CDK activity was paralleled by increased hypophosphorylation of Rb protein . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In both p 16 / and + / + cells , expression of Tax has been correlated with an increase in CDK 4 activity , which subsequently increases the phosphorylation of Rb and drives the infected cells into cell cycle progression . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In our study , we screened HCCs resulting from HCV infection ( 51 cases ) , HBV infection ( 26 cases ) or excess alcohol intake ( 23 cases ) for alterations in genes involved in the RB 1 pathway ( p 16 ( INK4a ) , p 15 ( INK4b ) , RB 1 , CDK 4 and cyclin D 1 ) , the p 53 pathway ( p 53 , p 14 ( ARF ) and MDM 2 ) and the Wnt pathway ( beta catenin , APC ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The effect of antisense EGFR on cell cycle was studied by flow cytometry and immunohistochemical analysis of p 53 , Rb , p 16 and CDK 4 expressions . ^^^ In addition , immunohistochemical analysis showed that the expression of wild type p 53 was significantly increased in the antisense EGFR cDNA transfected clones , whereas the expressions of Rb , p 16 and CDK 4 were not altered . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
We examined the role of retinoblastoma susceptibility gene ( RB 1 ) and the CDK 4 gene in human pituitary tumorigenesis . ^^^ Based on these results , it is concluded that somatic mutations of the RB 1 gene or CDK 4 gene do not appear to play a major role in pituitary tumorigenesis . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
When telomerase activity was correlated with the gene product based immunophenotypic profile of individual tumours , it was found that the absence of telomerase activity was associated with a lack of bcl 2 , p 53 , and c kit expression , and characterized by a low proliferation index consistent with the absence of cdk 4 expression and the presence of the cdk inhibitor Rb . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
These included 3 genes coding for proteins in the p 53 pathway ( i . e . , TP 53 , p 14 ( ARF ) , and MDM 2 ) , 4 in the Rb 1 pathway ( i . e . , CDKN2A , CDKN2B , RB 1 , and CDK 4 ) , as well as PTEN and epidermal growth factor receptor . ^^^ RESULTS : We found that abnormalities in any of the four genes ( CDKN2A , CDKN2B , RB 1 , and CDK 4 ) coding for components of the Rb 1 pathway were associated with shorter survival ( P = 0 . 002 ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
This effect was accompanied by the decreased expression of G ( 1 ) associated proteins including cyclin D 1 , CDK 4 , and Rb phosphorylation at Ser 780 , Ser 795 , and Ser807 / 811 , whereas expression of CDK 6 and beta actin was not affected by LY 294002 . ^^^ The mTOR inhibitor rapamycin has similar inhibitory effects on G ( 1 ) cell cycle progression and expression of cyclin D 1 , CDK 4 , and Rb phosphorylation . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
CDK 2 and CDK 4 known promoter of cell cycling catalyze phosphorylation of RB protein . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
IGF 1 also elicited a rapid time dependent increase in Rb ( Ser807 / 811 ) phosphorylation , the specific target of the cyclin D ( 1 ) dependent CDK 4 kinase , and a slower increase in total Rb protein levels . ^^^ Effects of IGF 1 on proliferation are mediated jointly by ERK1 / 2 dependent and PI 3 kinase dependent pathways that regulate cyclin D 1 levels , CDK 4 activity , and Rb activity . . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Inhibition of cdk 4 activity by GA was observed 3 hr after addition of the drug to late G ( 1 ) cells but not after a short ( 1 hr ) exposure , as revealed by the phosphorylation of Rb on the Ser ( 780 ) residue . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Expression patterns of regulatory proteins such as p 53 , cyclin D 1 , p 16 , Cdk 4 , p 21 , Rb , bcl 2 and PCNA were determined by immunohistochemistry utilizing monoclonal antibodies in 125 patients who received curative radiotherapy dose . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In rasREF cells treated with DE for 72 h in suspension culture ( a ) , the levels of cyclin D 1 , cyclin A , p 27 ( Kip 1 ) , and hyperphosphorylated Rb were decreased , but the levels of cdk 4 , cdk 6 , cdk 2 , p 16 ( INK4a ) , and p 21 ( Cip 1 ) were not affected . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Besides overexpression of cyclin D 1 , the cyclin dependent kinases ( CDK 2 and CDK 4 ) are highly expressed in MCL resulting in the phosphorylation of RB 1 , E2F release , and the cell cycle progression . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Furthermore , forced overexpression of only cdk 4 or cyclin D 1 induced apoptosis in cultured cells with normal Rb protein , whereas overexpression of any cyclin or cdk induced apoptosis in cells defective for Rb protein . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
METHODS : cdk 2 kinase assay to examine histone H 1 phosphorylation . cdk 4 kinase assay to examine whether active cdk 4 / cyclin D complexes , capable of phosphorylating Rb , are formed . ^^^ RESULTS : cdk 4 kinase mediated Rb phosphorylation was increased by AAF treatment . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Altered mRNA expression of the Rb and p 16 tumor suppressor genes and of CDK 4 in transitional cell carcinomas of the urinary bladder associated with tumor progression . ^^^ Based on the concept that tumor suppressor genes are involved in the pathogenesis of urinary bladder carcinogenesis , we analysed the mRNA expression of the retinoblastoma ( Rb ) and p 16 ( CDKN 2 , INK4A , MTS 1 ) genes as well as of the proto oncogene cyclin D dependent kinase 4 ( CDK 4 ) in 71 transitional cell carcinomas ( TCC ) of the urinary bladder in relation to the tumor grades and stages , and with reference to certain lifestyle and occupational risk factors . ^^^ Using real time quantitative reverse transcription polymerase chain reaction , high stage muscle invasive TCC expressed the Rb , p 16 and CDK 4 mRNA at lower levels than low stage superficial cancers , indicating down regulation to be linked with tumor progression . ^^^ Among occupational exposures , TCC of patients in contact with stone dust , paints and lacquer , plastics , wood and wood preservers and chemical solvents and adhesives displayed altered partly elevated , partly reduced levels of Rb , p 16 and CDK 4 mRNA compared to non exposed subjects . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Docking dependent regulation of the Rb tumor suppressor protein by Cdk 4 . ^^^ A novel Cdk 4 docking motif has been defined within a stretch of 19 amino acids from the C terminal domain of the Rb protein that are essential for Cdk 4 binding . ^^^ Mutation or deletion of the docking motif prevents Cdk 4 dependent phosphorylation of full length Rb protein or C terminal Rb fragments in vitro and in cells , while a peptide encompassing the Cdk 4 docking motif specifically inhibits Cdk 4 dependent phosphorylation of Rb . ^^^ Cyclin D 1 Cdk4 can overcome the growth suppressive activity of Rb in both cell cycle progression and colony formation assays ; however , while mutants of Rb in which the Cdk 4 docking site has been either deleted or mutated retain growth suppressor activity , they are resistant to inactivation by cyclin D 1 Cdk4 . ^^^ Finally , binding of Cdk 4 to its docking site can inhibit cleavage of exogenous and endogenous Rb in response to distinct apoptotic signals . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The ability of cyclin D 1 associated CDK 4 to phosphorylate retinoblastoma ( Rb ) protein was , however , reduced in the same cells . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In contrast , CDK 4 and Rb are not important in ovarian cancer cell growth inhibition . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The ability of integrins to induce the activation of EGFR and its subsequent regulation of Erk and Akt activation permitted adhesion dependent induction of cyclin D 1 and p 21 , Rb phosphorylation , and activation of cdk 4 in epithelial cells in the absence of exogenous growth factors . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Activated Notch inhibits mitogen induced upregulation of p21Cip1 and delays cyclin D cdk 4 mediated Rb phosphorylation . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Cyclin D 1 , D 2 and D 3 , and Cdk 4 , Cdk 6 and Rb protein , and Cyclin D 1 mRNA expression were measured in primary patient derived neuroblastoma cell lines . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The p16INK4a tumor suppressor protein functions as an inhibitor of CDK 4 and CDK 6 , the D type cyclin dependent kinases that initiate the phosphorylation of the retinoblastoma tumor suppressor protein , RB . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
RESULTS : In the transgenic mice , total CDK 4 protein expression was increased by up to 5 fold , with a concomitant increase in CDK 4 activity indicated by the detection of phosphorylated Rb protein in pancreatic islets . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Rb deleted myotubes were efficiently reactivated by forced expression of cyclin D 1 and Cdk 4 , indicating a functionally significant target other than pRb for these molecules . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Furthermore , atRA treatment reduced phosphorylated Rb and decreased cdk 2 and cdk 4 kinase activity . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
RB pathway mutations , especially at the CDK 4 and INK4A loci , are hallmarks of melanomagenesis . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
A reduction in cdk 4 protein levels is also observed with a parallel reduction in Rb phosphorylation levels at Ser 780 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Altered expression of cell cycle regulators Cyclin D 1 , p 14 , p 16 , CDK 4 and Rb in nodular melanomas . ^^^ To investigate whether alterations in Cyclin D 1 , p 14 , CDK 4 and Rb are associated with tumour cell proliferation , tumour progression and patient survival in malignant melanoma , we examined 202 vertical growth phase tumours and 68 corresponding metastases for expression of Cyclin D 1 , p 14 , CDK 4 and Rb , and compared the results with Ki 67 expression , p 16 and p 53 expression , clinico pathological variables , and survival data . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Expression of S100B in PC 12 cells resulted in activation of Akt ; increased levels of p21WAF1 , an inhibitor of cyclin dependent kinase ( cdk ) 2 and a positive regulator of cdk 4 ; increased p21WAF1 cyclin D 1 complex formation ; and increased phosphorylation of the retinoblastoma suppressor protein , Rb . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In addition , the Ras / PI3 K / AKT / Rac / NFkappaB / cyclin D 1 signaling cascade triggered by endogenously released IGF 1 is sufficient to sustain Rb phosphorylation and cdk 4 kinase activity in BON cells . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
TNFalpha reduced the transcripts and protein levels of phosphorylated retinoblastoma protein ( Rb ) , Rb , E2F1 , and Cdk 4 only in drug resistant p 35 colo201 cells . ^^^ This effect of TNFalpha was reversed by IKK inhibitor , suggesting that TNFalpha induced cell cycle arrest is probably due to the reduction of Rb , E2F1 , and Cdk 4 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Rb family members were the only demonstrated substrates of CDK 4 until it was shown recently that Smad 3 , which plays a key role in mediating TGF beta antiproliferative responses , is phosphorylated by both CDK 4 and CDK 2 in vivo and in vitro . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
All tumor samples expressed normal sized RB 1 , cyclin D 3 , CDK 2 , CDK 4 , p 21 ( CIP 1 ) , and p 27 ( KlP 1 ) proteins , and only a single tumor showed an aberrant protein band for one of these proteins , p 21 ( CIP 1 ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The expression pattern of key molecules of the Rb and p 53 pathways , such as Rb , cyclin D 1 , CDK 4 , p 16 , p 53 , p 21 and Bcl 2 and the proliferative marker PCNA were analysed in 348 oral carcinoma specimens by immunohistochemical technique . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
METHODS : Synovial tissue from 20 patients with active proliferative RA and 28 patients with RA in remission was immunohistochemically examined for expression of p 53 , p 63 , p 21 , p 27 , p 16 , cyclin D 1 , CDK 4 , RB , E2F , Ki 67 on tissue microarrays and by DNA flow cytometry for cell cycle phases . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Indeed , this phosphorylation was observed 6 hours after p 25 induction and was abolished in the presence of a Cdk 5 inhibitor , roscovitine , which does not inhibit the usual Rb cyclin D kinases Cdk 4 and Cdk 6 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The data suggest that the redundancy in phosphorylation of RB by CDK 2 and CDK 4 in Nalm 6 extracts is limited . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Role of cdk 4 , p16INK4 , and Rb expression in the prognosis of bronchioloalveolar carcinomas . ^^^ BACKGROUND : The p 16 ( INK 4 ) protein has been identified as a potent inhibitor of cyclin dependent kinase ( cdk ) 4 by blocking cdk 4 mediated phosphorylation of the tumor suppressor retinoblastoma ( Rb ) protein , thus allowing Rb mediated growth suppression . ^^^ METHODS : We examined immunohistochemical expression of p 16 ( INK 4 ) , cdk 4 , and Rb proteins in 38 BACs and correlated their expression levels with known clinicopathological features of the disease . ^^^ RESULTS : All BACs expressed cdk 4 , while 89 and 82 % expressed p 16 ( INK 4 ) and Rb proteins , respectively . ^^^ None of the clinicopathological factors correlated with p 16 ( INK 4 ) , cdk 4 , or Rb expression separately . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Melanomas also commonly show impairment of the p 16 ( INK4A ) CDK 4 Rb and ARF HDM 2 p53 tumor suppressor pathways . ^^^ Rb bypass can also occur through activating CDK 4 mutations as well as by CDK 4 amplification . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
These included three genes coding for proteins in the p 53 pathway ( TP 53 , p 14 ( ARF ) and MDM 2 ) , four in the Rb 1 pathway ( CDKN2A , CDKN2B , RB 1 and CDK 4 ) and PTEN and EGFR . ^^^ We found that loss of both wild type copies of any of the three tumour suppressor genes CDKN2A , CDKN2B and RB 1 or gene amplification of CDK 4 , disrupting the Rb 1 pathway , were associated with shorter survival ( P=0 . 009 ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Moreover , the upregulation of p 21 was followed by the inactivations of cdk 4 and cdk 2 , the hypophosphorylation of Rb , and a marked decline in the expression of c myc ( a gene regulated by E2F that is a transcription factor whose activity is suppressed when it is bound to hypophosphorylated Rb ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The increases in myotube hypertrophy and RNA content were blocked by rapamycin treatment , which also prevented the increase in cyclin D 1 protein expression , CDK 4 activity , Rb phosphorylation , and the increase in UBF availability . ^^^ Our findings demonstrate that activation of mTOR is necessary for myotube hypertrophy and suggest that the role of mTOR is in part to modulate cyclin D 1 dependent CDK 4 activity in the regulation of Rb and ribosomal RNA synthesis . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
In this study , using exogenous wild type P 16 gene , antibodies for P 16 , Cdk 4 , Cyclin D 1 and Rb proteins , and primers for these genes , we examined the expression of exogenous wild type P 16 gene and the changes of cell cycle regulatory genes ( Cdk 4 , Cyclin D 1 , and Rb ) in human bladder cancer cells . ^^^ The immunocytochemical results indicated that after the transfection of exogenous wild type P 16 gene , the expression of Cdk 4 , Cyclin D 1 , and Rb were negative in the nuclei , whereas the expression of P 16 significantly increased in the nuclei and the cytoplasm . ^^^ The RT PCR results showed that the transcription of P 16 gene increased significantly after the transfection , whereas the transcription of Cdk 4 , Cyclin D 1 , and Rb decreased . ^^^ Our results suggest that the transfection of exogenous wild P 16 gene induces the bladder cancer cells arrested in G0 / G1 phase , and the increasing expression of P 16 inhibits the expression of Cdk 4 , Cyclin D 1 , and Rb in nuclei . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Here we report that in prototype small intestine crypt stem cells ( RIEC 6 ) , stimulation with either epidermal growth factor or fetal bovine serum results in an unexpected rapid and sustained Rb phosphorylation at sites Ser 780 , Ser 795 , and Thr 821 which precedes cyclin D 1 expression , cyclin D1 / cdk4 complex formation , and cdk 4 kinase activity . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
EXPERIMENTAL DESIGN : We determined the mRNA expression of p 1 ( INK4A ) , p 14 ( ARF ) , CDK 4 , RB 1 , MDM 2 , TP 53 , and E2F1 by quantitative reverse transcription PCR in 38 cases of GISTs and correlated the findings with clinicopathologic factors , including mutation analysis of KIT and PDGFRA . ^^^ GISTs with low mRNA expression of the CDKN2A transcripts p 16 ( INK4A ) and p 14 ( ARF ) but high mRNA expression of CDK 4 , RB 1 , MDM 2 , TP 53 , and E2F1 were associated with aggressive clinical behavior and unfavorable prognosis , whereas GISTs with a low mRNA expression of CDK 4 , RB 1 , MDM 2 , TP 53 , and E2F1 were not . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Gankyrin also binds to CDK 4 and the tumor suppressor RB , and accelerates phosphorylation and proteasomal degradation of RB . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Down regulation of cell cycle regulatory components ( CDK 4 , cyclin B , E2F , and phosphorylated Rb ) were observed under similar conditions . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
After analyzing the cellular proteins involving in regulation of cell cycle progression , we demonstrated that ORF7a expression was correlated with a significant reduction of cyclin D 3 level of mRNA transcription and expression , and phosphorylation of retinoblastoma ( Rb ) protein at ser 795 and ser809 / 811 , not with the expression of cyclin D 1 , D 2 , cdk 4 and cdk 6 in HEK 293 cells . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The kinase activity for cyclins D 1 and D 3 , using retinoblastoma ( Rb ) as a substrate , in E ( 2 ) induced MGTs and their binding to cdk 4 was significantly elevated . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Inhibition of endogenous cyclin D 1 or CDK 4 expression by RNA interference resulted in hypophosphorylation of RB and accumulation of cells in G 1 . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
We thus set out to assess how recurrent patterns of genetic injury at three critical human melanoma loci CDKN2A , TP 53 , and CDK 4 cooperate to disrupt both RB and p 53 pathways . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Analysis of mRNA and protein levels in melanomas with 12q14 amplification demonstrated overexpression of target genes CDK 4 and MDM 2 without loss of CDKN2A P 16 ( P16INK4A ) or CDKN2A P14ARF ( P14ARF ) expression , important regulators of the RB 1 and TP 53 pathways , which are commonly lost or mutated in melanoma . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
After epidermal growth factor stimulation , p28GANK protein was up regulated in oval cells from 24 to 72 h , which coincided with increased expression of CyclinD 1 , CDK 4 and decreased of Rb protein . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Many mechanisms may be responsible for activating the RB Cyclin D 1 pathway , including activating ( CDK 4 ) and inactivating mutations ( p16INK4A ) , deletions ( RB and p16INK4A ) , amplifications ( CCND 1 and CDK 4 ) , silencing methylation ( p16INK4A and RB ) , and hyper phosphorylation ( RB ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Combined loss of Cdk 2 and Cdk 4 results in embryonic lethality and Rb hypophosphorylation . ^^^ Our results demonstrate that Cdk 2 and Cdk 4 cooperate to phosphorylate Rb in vivo and to couple the G1 / S phase transition to mitosis via E2F dependent regulation of gene expression . . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Cell lines and tissue samples displayed constitutive activation of the cyclin D 1 signaling cascade , as evidenced by strong expression of CDK 4 , Rb phosphorylation , and cyclin D1 / CDK4 coassociation . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Immunohistochemical stains were carried out on tissue microarrays to evaluate the expression of proteins involved in the G ( 1 ) S transition and proteins that regulate apoptosis including Rb , E2F1 , cyclin D 1 , CDK 4 , CDK 6 , p 27 ( KIP 1 ) , p 21 ( WAF1 / CIP1 ) , p 53 , Mdm 2 , Bcl 2 , and Bax . ^^^ The positive phenotypes identified were as follows : Rb , 39 . 1 % ; E2F1 , 69 . 6 % ; cyclin D 1 , 30 . 4 % ; CDK 4 , 100 % ; CDK 6 , 30 . 4 % ; 39 . 1 % ; p 27 ( KIP 1 ) , 47 . 8 % ; p 21 ( WAF1 / CIP1 ) , 39 . 1 % ; p 53 , 43 . 5 % ; Mdm 2 , 17 . 4 % ; Bcl 2 , 91 . 3 % ; and Bax , 100 % . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
The remaining wild type allele of Pten was lost at a high frequency in Pten+ / cells but not in p18+ / Pten+ / or p 18 / Pten+ / prostate tumor cells , nor in other Pten+ / tumor cells , suggesting a tissue and genetic background dependent haploinsufficiency of Pten in tumor suppression . p 18 deletion , CDK 4 overexpression , or oncoviral inactivation of Rb family proteins caused activation of Akt / PKB that was recessive to the reduction of PTEN activity . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
METHODS : Genes for the CDKIs p 16 ( INK4a ) and p 18 ( INK4c ) , a constitutively active form of retinoblastoma ( RB ) gene product , cyclin D 1 , and CDK 4 , were transferred into RA synovial fibroblasts ( RASFs ) . ^^^
Interacting proteins: P11802 and P06400	Pubmed	SVM Score :0.0
Membrane depolarization induced by 50 mM KCl for 5 min significantly increased SH SY5Y cell numbers and thymidine incorporation at 24 h after depolarization , and increased the phosphorylation and expression of retinoblastoma protein ( RB ) , the activity of Cdk 2 ( without changing the activities of Cdk 4 and Cdk 6 ) , and the expressions of cyclin A and cyclin E . ^^^