| BUB3 that dissociates from BUB1 activates caspase-independent mitotic death (CIMD). | |
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MedLine Citation:
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PMID: 20057499 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Y Niikura; H Ogi; K Kikuchi; K Kitagawa |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-01-08 |
Journal Detail:
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Title: Cell death and differentiation Volume: 17 ISSN: 1476-5403 ISO Abbreviation: Cell Death Differ. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-10 Completed Date: 2010-07-08 Revised Date: 2011-05-13 |
Medline Journal Info:
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Nlm Unique ID: 9437445 Medline TA: Cell Death Differ Country: England |
Other Details:
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Languages: eng Pagination: 1011-24 Citation Subset: IM |
Affiliation:
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Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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