Regulation of CDK4 activity by a novel CDK4-binding protein, p34(SEI-1).
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.
Mesh Terms:
Animals, Blood Physiological Phenomena, COS Cells, Carrier Proteins, Cell Cycle, Cells, Cultured, Cercopithecus aethiops, Chromosomes, Human, Pair 19, Culture Media, Serum-Free, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinases, DNA, Complementary, Enzyme Activation, Fibroblasts, Genes, Hela Cells, Humans, Nuclear Proteins, Proto-Oncogene Proteins, Saccharomyces cerevisiae, Trans-Activators, Transfection, Two-Hybrid System Techniques
Animals, Blood Physiological Phenomena, COS Cells, Carrier Proteins, Cell Cycle, Cells, Cultured, Cercopithecus aethiops, Chromosomes, Human, Pair 19, Culture Media, Serum-Free, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinases, DNA, Complementary, Enzyme Activation, Fibroblasts, Genes, Hela Cells, Humans, Nuclear Proteins, Proto-Oncogene Proteins, Saccharomyces cerevisiae, Trans-Activators, Transfection, Two-Hybrid System Techniques
Genes Dev.
Date: Nov. 15, 1999
PubMed ID: 10580009
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