Abstract
The cyclin-dependent kinase 4 (CDK4) regulates progression through the G1 phase of the cell cycle. The activity of CDK4 is controlled by the opposing effects of the D-type cyclin, an activating subunit, and p16INK4, an inhibitory subunit. Ectopic expression of p16INK4 blocked entry into S phase of the cell cycle induced by oncogenic Ha-Ras, and this block was relieved by coexpression of a catalytically inactive CDK4 mutant. Expression of p16INK4 suppressed cellular transformation of primary rat embryo fibroblasts by oncogenic Ha-Ras and Myc, but not by Ha-Ras and E1a. Together, these observations provide direct evidence that p16INK4 can inhibit cell growth.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenovirus E1A Proteins / genetics
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Adenovirus E1A Proteins / physiology
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / physiology*
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Cell Division*
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Cell Transformation, Neoplastic*
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Cells, Cultured
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclin-Dependent Kinases*
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Genes, Reporter
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Genes, Retinoblastoma
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Genes, myc
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Genes, ras
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Plasmids
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins*
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Rats
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Retinoblastoma Protein / physiology
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S Phase
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Transcriptional Activation
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Transfection
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Tumor Cells, Cultured
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ras Proteins / genetics
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ras Proteins / physiology*
Substances
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Adenovirus E1A Proteins
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Carrier Proteins
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Cyclin-Dependent Kinase Inhibitor p16
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Proto-Oncogene Proteins
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Retinoblastoma Protein
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Protein Serine-Threonine Kinases
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Cdk4 protein, rat
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinases
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ras Proteins