Regulation of CDK4 activity by a novel CDK4-binding protein, p34(SEI-1).
Sugimoto M,
Nakamura T,
Ohtani N,
Hampson L,
Hampson IN,
Shimamoto A,
Furuichi Y,
Okumura K,
Niwa S,
Taya Y,
Hara E.
Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, M20 4BX, UK.
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