Document Detail


BUB3 that dissociates from BUB1 activates caspase-independent mitotic death (CIMD).
MedLine Citation:
PMID:  20057499     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cell death mechanism that prevents aneuploidy caused by a failure of the spindle checkpoint has recently emerged as an important regulatory paradigm. We previously identified a new type of mitotic cell death, termed caspase-independent mitotic death (CIMD), which is induced during early mitosis by partial BUB1 (a spindle checkpoint protein) depletion and defects in kinetochore-microtubule attachment. In this study, we have shown that survived cells that escape CIMD have abnormal nuclei, and we have determined the molecular mechanism by which BUB1 depletion activates CIMD. The BUB3 protein (a BUB1 interactor and a spindle checkpoint protein) interacts with p73 (a homolog of p53), specifically in cells wherein CIMD occurs. The BUB3 protein that is freed from BUB1 associates with p73 on which Y99 is phosphorylated by c-Abl tyrosine kinase, resulting in the activation of CIMD. These results strongly support the hypothesis that CIMD is the cell death mechanism protecting cells from aneuploidy by inducing the death of cells prone to substantial chromosome missegregation.
Authors:
Y Niikura; H Ogi; K Kikuchi; K Kitagawa
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-01-08
Journal Detail:
Title:  Cell death and differentiation     Volume:  17     ISSN:  1476-5403     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-10     Completed Date:  2010-07-08     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  1011-24     Citation Subset:  IM    
Affiliation:
Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Caspases / genetics,  physiology
Cell Cycle Proteins / metabolism*
Cell Death / physiology*
Cell Nucleus / ultrastructure
Cell Survival
DNA-Binding Proteins / genetics,  metabolism
HeLa Cells
Humans
Mice
Mice, Knockout
Mitosis*
Nuclear Proteins / genetics,  metabolism
Protein Isoforms / physiology
Protein-Serine-Threonine Kinases / metabolism*
Proto-Oncogene Proteins c-abl / metabolism
Tumor Suppressor Proteins / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
CA21765/CA/NCI NIH HHS; GM68418/GM/NIGMS NIH HHS; R01 GM068418-06A2/GM/NIGMS NIH HHS; R01 GM068418-08/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/BUB3 protein, human; 0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/Nuclear Proteins; 0/Protein Isoforms; 0/Tumor Suppressor Proteins; 0/tumor suppressor protein p73; EC 2.7.10.2/Proto-Oncogene Proteins c-abl; EC 2.7.11.1/Bub1 spindle checkpoint protein; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 3.4.22.-/Caspases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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