Abstract
The p16(INK4a) tumor suppressor inhibits cyclin-dependent kinases (CDK4 and CDK6). Here we report the isolation of a novel gene, SEI-1, whose product (p34(SEI-1)) appears to antagonize the function of p16(INK4a). Addition of p34(SEI-1) to cyclin D1-CDK4 renders the complex resistant to inhibition by p16(INK4a). Expression of SEI-1 is rapidly induced on addition of serum to quiescent fibroblasts, and ectopic expression of p34(SEI-1) enables fibroblasts to proliferate even in low serum concentrations. p34(SEI-1) seems to act as a growth factor sensor and may facilitate the formation and activation of cyclin D-CDK complexes in the face of inhibitory levels of INK4 proteins.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood Physiological Phenomena
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COS Cells
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Carrier Proteins / physiology*
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Cell Cycle / physiology
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Cells, Cultured
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Chlorocebus aethiops
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Chromosomes, Human, Pair 19 / genetics
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Culture Media, Serum-Free
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinase Inhibitor p16 / antagonists & inhibitors
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Cyclin-Dependent Kinases / metabolism*
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DNA, Complementary / genetics
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Enzyme Activation
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Fibroblasts / drug effects
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Fibroblasts / enzymology
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Genes
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HeLa Cells
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Humans
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Nuclear Proteins*
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Proto-Oncogene Proteins*
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Saccharomyces cerevisiae
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Trans-Activators*
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Transcription Factors
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Transfection
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Two-Hybrid System Techniques
Substances
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Carrier Proteins
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Culture Media, Serum-Free
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Cyclin-Dependent Kinase Inhibitor p16
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DNA, Complementary
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Nuclear Proteins
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Proto-Oncogene Proteins
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SERTAD1 protein, human
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Trans-Activators
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Transcription Factors
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CDK4 protein, human
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinases