Regulation of CDK4 activity by a novel CDK4-binding protein, p34SEI-1
- Masataka Sugimoto,
- Takeshi Nakamura,
- Naoko Ohtani,
- Lynne Hampson,
- Ian N. Hampson,
- Akira Shimamoto,
- Yasuhiro Furuichi,
- Ko Okumura,
- Shinichiro Niwa,
- Yoichi Taya, and
- Eiji Hara
- Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, M20 4BX, UK; Juntendo University School of Medicine, Tokyo, Japan; Sumitomo Electric Industries, Yokohama, Japan; St. Mary's Hospital, Manchester, UK; Agene Research Institute, Kamakura, Japan; National Cancer Center Research Institute, Tokyo, Japan
Abstract
The p16INK4a tumor suppressor inhibits cyclin-dependent kinases (CDK4 and CDK6). Here we report the isolation of a novel gene, SEI-1, whose product (p34SEI-1) appears to antagonize the function of p16INK4a. Addition of p34SEI-1 to cyclin D1–CDK4 renders the complex resistant to inhibition by p16INK4a. Expression of SEI-1 is rapidly induced on addition of serum to quiescent fibroblasts, and ectopic expression of p34SEI-1 enables fibroblasts to proliferate even in low serum concentrations. p34SEI-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.
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Footnotes
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↵Corresponding author.
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E-MAIL Ehara{at}picr.man.ac.uk; FAX +44-161-446-3109.
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- Received May 10, 1999.
- Accepted September 23, 1999.
- Cold Spring Harbor Laboratory Press