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Genes Dev. 1999 Nov 15;13(22):3027-33.

Regulation of CDK4 activity by a novel CDK4-binding protein, p34(SEI-1).

Author information

  • 1Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, M20 4BX, UK.

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.

PMID:
10580009
[PubMed - indexed for MEDLINE]
PMCID:
PMC317153
Free PMC Article
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