Regulation of the cell cycle at the G1-S transition by proteolysis of cyclin E and p27Kip1

Kei Ichi Nakayama, Shigetsugu Hatakeyama, Keiko Nakayama

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190 Citations (Scopus)

Abstract

The transition from G1 phase to S phase of the mammalian cell cycle is controlled by many positive and negative regulators, among which cyclin E and p27Kip1, respectively, undergo the most marked changes in concentration at this transition. The abundance of both cyclin E and p27Kip1 is regulated predominantly by posttranslational mechanisms, in particular by proteolysis mediated by the ubiquitin-proteasome pathway. Cyclin E and p27Kip1 each bind to and undergo polyubiquitination by the same ubiquitin ligase, known as SCFSkp2. The degradation of cyclin E and p27Kip1 is greatly impaired in Skp2-deficient mice, resulting in intracellular accumulation of these proteins. In this article, recent progress in characterization of the molecular mechanisms that control the proteolysis of cyclin E and p27Kip1 is reviewed.

Original languageEnglish
Pages (from-to)853-860
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume282
Issue number4
DOIs
Publication statusPublished - Jan 1 2001

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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