Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex

Wenyi Wei, Nagi G. Ayad, Yong Wan, Guo Jun Zhang, Marc W. Kirschner, William G. Kaelin

Research output: Contribution to journalArticlepeer-review

358 Scopus citations

Abstract

Cell-cycle transitions are driven by waves of ubiquitin-dependent degradation of key cell-cycle regulators. SCF (Skp1/Cullin/F-box protein) complexes and anaphase-promoting complexes (APC) represent two major classes of ubiquitin ligases whose activities are thought to regulate primarily the G1/S and metaphase/anaphase cell-cycle transitions, respectively. The major target of the Skp1/Cul1/Skp2 (SCFSKP2) complex is thought to be the Cdk inhibitor p27 during S phase, whereas the principal targets for the APC are thought to be involved in chromatid separation (securin) and exit from mitosis (cyclin B). Although the role of the APC in mitosis is relatively clear, there is mounting evidence that APCs containing Cdh1 (APCCDH1) also have a function in the G1 phase of the cell cycle. Here, we show that the F-box protein Skp2 is polyubiquitinated, and hence earmarked for destruction, by APCCDH1. As a result, accumulation of SCFSKP2 requires prior inactivation of APCCDH1. These findings provide an insight into the orchestration of SCF and APC activities during cell-cycle progression, and into the involvement of the APC in G1.

Original languageEnglish (US)
Pages (from-to)194-198
Number of pages5
JournalNature
Volume428
Issue number6979
DOIs
StatePublished - Mar 11 2004
Externally publishedYes

ASJC Scopus subject areas

  • General

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