Document Detail


p31(comet) acts to ensure timely spindle checkpoint silencing subsequent to kinetochore attachment.
MedLine Citation:
PMID:  21965286     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The spindle assembly checkpoint links the onset of anaphase to completion of chromosome-microtubule attachment and is mediated by the binding of Mad and Bub proteins to kinetochores of unattached or maloriented chromosomes. Mad2 and BubR1 traffic between kinetochores and the cytosol, thereby transmitting a "wait anaphase" signal to the anaphase-promoting complex. It is generally assumed that this signal dissipates automatically upon kinetochore-microtubule binding, but it has been shown that under conditions of nocodazole-induced arrest p31(comet), a Mad2-binding protein, is required for mitotic progression. In this article we investigate the localization and function of p31(comet) during normal, unperturbed mitosis in human and marsupial cells. We find that, like Mad2, p31(comet) traffics on and off kinetochores and is also present in the cytosol. Cells depleted of p31(comet) arrest in metaphase with mature bipolar kinetochore-microtubule attachments, a satisfied checkpoint, and high cyclin B levels. Thus p31(comet) is required for timely mitotic exit. We propose that p31(comet) is an essential component of the machinery that silences the checkpoint during each cell cycle.
Authors:
Robert S Hagan; Michael S Manak; Håkon Kirkeby Buch; Michelle G Meier; Patrick Meraldi; Jagesh V Shah; Peter K Sorger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-09-30
Journal Detail:
Title:  Molecular biology of the cell     Volume:  22     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-17     Completed Date:  2012-05-17     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4236-46     Citation Subset:  IM    
Affiliation:
Center for Cell Decision Processes, Harvard Medical School, Boston, MA 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / metabolism*
Animals
Calcium-Binding Proteins / metabolism
Cell Cycle* / drug effects
Cell Cycle Proteins / metabolism*
Cell Line
Chromosomes, Human / metabolism
Chromosomes, Mammalian / metabolism
Cyclin B / analysis
Cytosol
Humans
Kinetochores / metabolism*
M Phase Cell Cycle Checkpoints*
Microtubules / metabolism
Mitosis / drug effects
Mitotic Spindle Apparatus / metabolism
Nocodazole / pharmacology
Nuclear Proteins / metabolism*
Potoroidae
Protein Transport
Protein-Serine-Threonine Kinases / metabolism
RNA Interference
Repressor Proteins / metabolism
Signal Transduction
Tubulin Modulators / pharmacology
Grant Support
ID/Acronym/Agency:
CA084179/CA/NCI NIH HHS; GM51464/GM/NIGMS NIH HHS; GM77238/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Calcium-Binding Proteins; 0/Cell Cycle Proteins; 0/Cyclin B; 0/MAD2L1 protein, human; 0/MAD2L1BP protein, human; 0/Nuclear Proteins; 0/Repressor Proteins; 0/Tubulin Modulators; 31430-18-9/Nocodazole; EC 2.7.11.1/Bub1 spindle checkpoint protein; EC 2.7.11.1/Protein-Serine-Threonine Kinases
Comments/Corrections

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