Control of mitotic transitions by the anaphase-promoting complex

Guowei Fang, Hongtao Yu, Marc W. Kirschner

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Proteolysis controls key transitions at several points in the cell cycle. In mitosis, the activation of a large ubiquitin-protein ligase, the anaphase-promoting complex (APC), is required for anaphase initiation and for exit from mitosis. We show that APC is under complex control by a network of regulatory factors, CDC20, CDH1 and MAD2. CDC20 and CDH1 are activators of APC; they bind directly to APC and activate its cyclin ubiquitination activity. CDC20 activates APC at the onset of anaphase in a destruction box (DB)-dependent manner, while CDH1 activates APC from late anaphase through G1 with apparently a much relaxed specificity for the DB. Therefore, CDC20 and CDH1 control both the temporal order of activation and the substrate specificity of APC, and hence regulate different events during mitosis and G1. Counteracting the effect of CDC20, the checkpoint protein MAD2 acts as an inhibitor of APC. When the spindle-assembly checkpoint is activated, MAD2 forms a ternary complex with CDC20 and APC to prevent activation of APC, and thereby arrests cells at prometaphase. Thus, a combination of positive and negative regulators establishes a regulatory circuit of APC, ensuring an ordered progression of events through cell division.

Original languageEnglish (US)
Pages (from-to)1583-1590
Number of pages8
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume354
Issue number1389
Publication statusPublished - Sep 29 1999

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Keywords

  • Anaphase-promoting complex (APC)
  • CDC20
  • CDH1
  • MAD2
  • Protein degradation
  • Spindle-assembly checkpoint

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Agricultural and Biological Sciences (miscellaneous)

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