Defining pathways of spindle checkpoint silencing: functional redundancy between Cdc20 ubiquitination and p31(comet).

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 disassembles 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.
Authors	Luying Jia, Bing Li, Ross T Warrington, Xing Hao, Shixuan Wang, Hongtao Yu
Journal	Molecular biology of the cell (Mol Biol Cell) Vol. 22 Issue 22 Pg. 4227-35 (Nov 2011) ISSN: 1939-4586 [Electronic] United States
PMID	21937719 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Adaptor Proteins, Signal Transducing Calcium-Binding Proteins Cdc20 Proteins Cell Cycle Proteins MAD2L1 protein, human MAD2L1BP protein, human Mad2 Proteins Nuclear Proteins Repressor Proteins CDC20 protein, human Proteasome Endopeptidase Complex
Topics	Adaptor Proteins, Signal Transducing (genetics, metabolism) Anaphase (genetics) Calcium-Binding Proteins (metabolism) Cdc20 Proteins Cell Cycle Proteins (genetics, metabolism) HeLa Cells Humans Kinetochores (metabolism) M Phase Cell Cycle Checkpoints Mad2 Proteins Mitosis Nuclear Proteins (genetics, metabolism) Proteasome Endopeptidase Complex (metabolism) RNA Interference Repressor Proteins (metabolism) Spindle Apparatus (genetics, metabolism) Ubiquitination

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