SCF-mediated Cdh1 degradation defines a negative feedback system that coordinates cell-cycle progression

Hidefumi Fukushima, Kohei Ogura, Lixin Wan, Ying Lu, Victor Li, Daming Gao, Pengda Liu, Alan W. Lau, Tao Wu, Marc W. Kirschner, Hiroyuki Inuzuka, Wenyi Wei

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

Proper cell-cycle transitions are driven by waves of ubiquitin-dependent degradation of key regulators by the anaphase-promoting complex (APC) and Skp1-Cullin1-F-box (SCF) E3 ubiquitin ligase complexes. But precisely how APC and SCF activities are coordinated to regulate cell-cycle progression remains largely unclear. We previously showed that APC/Cdh1 earmarks the SCF component Skp2 for degradation. Here, we continue to report that SCFβ-TRCP reciprocally controls APC/Cdh1 activity by governing Cdh1 ubiquitination and subsequent degradation. Furthermore, we define both cyclin A and Plk1, two well-known Cdh1 substrates, as upstream modifying enzymes that promote Cdh1 phosphorylation to trigger Cdh1 ubiquitination and subsequent degradation by SCFβ-TRCP. Thus, our work reveals a negative repression mechanism for SCF to control APC, thereby illustrating an elegant dual repression system between these two E3 ligase complexes to create the ordered cascade of APC and SCF activities governing timely cell-cycle transitions

Original languageEnglish
Pages (from-to)803-816
Number of pages14
JournalCell Reports
Volume4
Issue number4
DOIs
Publication statusPublished - 2013 Aug 29

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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