Regulation of CDK4 activity by a novel CDK4-binding protein, p34SEI-1

  1. Masataka Sugimoto,
  2. Takeshi Nakamura,
  3. Naoko Ohtani,
  4. Lynne Hampson,
  5. Ian N. Hampson,
  6. Akira Shimamoto,
  7. Yasuhiro Furuichi,
  8. Ko Okumura,
  9. Shinichiro Niwa,
  10. Yoichi Taya, and
  11. Eiji Hara
  1. 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.

Keywords

Footnotes

  • Corresponding author.

  • E-MAIL Ehara{at}picr.man.ac.uk; FAX +44-161-446-3109.

    • Received May 10, 1999.
    • Accepted September 23, 1999.
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