Role of phosphorylation of Cdc20 in p31^sup comet^-stimulated disassembly of the mitotic checkpoint complex

The mitotic checkpoint system delays anaphase until all chromosomes are correctly attached to the mitotic spindle. When the checkpoint is turned on, it promotes the formation of the mitotic checkpoint complex (MCC), which inhibits the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C). MC...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2012-05, Vol.109 (21), p.8056
Main Authors: Miniowitz-Shemtov, Shirly, Eytan, Esther, Ganoth, Dvora, Sitry-Shevah, Danielle, Dumin, Elena, Hershko, Avram
Format: Article
Language:English
Subjects:
Adenosine triphosphatase
Chromosomes
Mutation
Phosphorylation
Proteins
Online Access:Get full text
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Summary:The mitotic checkpoint system delays anaphase until all chromosomes are correctly attached to the mitotic spindle. When the checkpoint is turned on, it promotes the formation of the mitotic checkpoint complex (MCC), which inhibits the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C). MCC is composed of the checkpoint proteins BubR1, Bub3, and Mad2 bound to the APC/C activator Cdc20. When the checkpoint is satisfied, MCC is disassembled and APC/C becomes active. Previous studies have shown that the Mad2-binding protein p31... promotes the dissociation of Cdc20 from BubR1 in MCC in a process that requires ATP. We now show that a part of MCC dissociation is blocked by inhibitors of cyclin-dependent kinases (Cdks) and that purified Cdk1-cyclin B stimulates this process. The mutation of all eight potential Cdk phosphorylation sites of Cdc20 partially prevented its release from BubR1. Furthermore, p31... stimulated Cdk-catalyzed phosphorylation of Cdc20 in MCC. It is suggested that the binding of p31... to Mad2 in MCC may trigger a conformational change in Cdc20 that facilitates its phosphorylation by Cdk, and that the latter process may promote its dissociation from BubR1. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:0027-8424
1091-6490