Defining pathways of spindle checkpoint silencing

Functional redundancy between Cdc20 ubiquitination and p31 comet

Luying Jia, Bing Li, Ross T. Warrington, Xing Hao, Shixuan Wang, Hongtao Yu

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The spindle checkpoint senses unattached or improperly attached kinetochores during mitosis, inhibits the anaphase-promoting complex or cyclosome (APC/C), and delays anaphase onset to prevent aneuploidy. The mitotic checkpoint complex (MCC) consisting of BubR1, Bub3, Mad2, and Cdc20 is a critical APC/C-inhibitory checkpoint complex in human cells. At the metaphase-anaphase transition, the spindle checkpoint turns off, and MCC dis-assembles to allow anaphase onset. The molecular mechanisms of checkpoint inactivation are poorly understood. A major unresolved issue is the role of Cdc20 autoubiquitination in this process. Although Cdc20 autoubiquitination can promote Mad2 dissociation from Cdc20, a nonubiquitinatable Cdc20 mutant still dissociates from Mad2 during checkpoint inactivation. Here, we show that depletion of p31 comet delays Mad2 dissociation from Cdc20 mutants that cannot undergo autoubiquitination. Thus both p31 comet and ubiquitination of Cdc20 are critical mechanisms of checkpoint inactivation. They act redundantly to promote Mad2 dissociation from Cdc20.

Original languageEnglish (US)
Pages (from-to)4227-4235
Number of pages9
JournalMolecular Biology of the Cell
Volume22
Issue number22
DOIs
StatePublished - Nov 15 2011

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Anaphase
Ubiquitination
Anaphase-Promoting Complex-Cyclosome
M Phase Cell Cycle Checkpoints
Kinetochores
Aneuploidy
Metaphase
Mitosis

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Defining pathways of spindle checkpoint silencing : Functional redundancy between Cdc20 ubiquitination and p31 comet. / Jia, Luying; Li, Bing; Warrington, Ross T.; Hao, Xing; Wang, Shixuan; Yu, Hongtao.

In: Molecular Biology of the Cell, Vol. 22, No. 22, 15.11.2011, p. 4227-4235.

Research output: Contribution to journalArticle

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