Document Detail


Involvement of p38alpha in the mitotic progression of p53(-/-) tetraploid cells.
MedLine Citation:
PMID:  20686359     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
The tumor suppressor protein p53 plays a major role in preserving genomic stability. p53 suppresses a pathway leading from normal diploidy to neoplastic aneuploidy (via an intermediate metastable stage of tetraploidy) at two levels: first by preventing the generation/survival of tetraploid cells, and second by repressing their aberrant multipolar division. Here, we report the characterization of p53(-/-) tetraploid cells, which-at difference with both their p53(-/-) diploid and their p53(+/+) tetraploid counterparts-manifest a marked hyperphosporylation of the mitogen-activated protein kinase MAPK14 (best known as p38alpha) that is particularly strong during mitosis. In p53(-/-) tetraploid cells, phosphorylated p38alpha accumulated at centrosomes during the metaphase and at midbodies during the telophase. Selective knockdown or pharmacological inhibition of p38alpha had a dramatic effect on p53(-/-) (but not p53(+/+)) tetraploids, causing the activation of the spindle assembly checkpoint, an arrest during the metaphase, a major increase in abnormal bipolar and monopolar mitoses, as well as an increment in the generation of multinuclear cells. We conclude that the mitotic progression of p53(-/-) (but not p53(+/+)) tetraploids heavily relies on p38alpha, revealing a novel function for this protein in the context of aneuploidizing cell divisions.
Authors:
Ilio Vitale; Mohamed Jemaà; Laura Senovilla; Lorenzo Galluzzi; Santiago Rello-Varona; Didier Metivier; Hugues Ripoche; Vladimir Lazar; Philippe Dessen; Maria Castedo; Guido Kroemer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-03
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  9     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-08-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2823-9     Citation Subset:  IM    
Affiliation:
INSERM, U848, Villejuif, France.
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Comment In:
Cell Cycle. 2010 Jul 15;9(14):2712   [PMID:  20676035 ]
Cell Cycle. 2010 Aug 1;9(15):2928   [PMID:  20703078 ]

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