Document Detail


BRCA1-IRIS overexpression abrogates UV-induced p38MAPK/p53 and promotes proliferation of damaged cells.
MedLine Citation:
PMID:  20622893     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cells' ability to evade cell death and to proliferate post geno-/cell-toxic stresses likely leads to formation of cancer. Activation of p38MAPK and p53 following these stresses helps protect cells against cancer development by initiating apoptosis. The duration of p38MAPK and p53 activation is regulated by the WIP1 phosphatase. BRCA1-IRIS triggers WIP1 expression in a p53-dependent and -independent manner. BRCA1-IRIS triggers the expression and cytoplasmic localization of the mRNA stabilization and translation inducer, HuR, that binds p53 and PPM1D mRNA. Hence, BRCA1-IRIS overexpression inactivates p38MAPK and/or p53 by upregulating WIP1 expression. BRCA1-IRIS abrogation of the homeostatic balance maintained by the p38MAPK-p53-WIP1 pathway suppressed cell death induced by a lethal dose of short-wavelength UV light, and high dosage of etoposide or H(2)O(2), and allowed cells to survive and proliferate post geno-/cell-toxic stresses. This mechanism represents a new link between geno-/cell-toxic stress and aggressive breast cancer formation in p53 wild-type cells.
Authors:
K Chock; J M S Allison; W M Elshamy
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-12
Journal Detail:
Title:  Oncogene     Volume:  29     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-24     Completed Date:  2010-10-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  5274-85     Citation Subset:  IM    
Affiliation:
Department of Pathology, John A Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Proliferation*
Etoposide / pharmacology
Gene Silencing
Genes, BRCA1*
Humans
Hydrogen Peroxide / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Transcription, Genetic
Tumor Suppressor Protein p53 / biosynthesis*
Ultraviolet Rays*
p38 Mitogen-Activated Protein Kinases / biosynthesis*
Chemical
Reg. No./Substance:
0/Tumor Suppressor Protein p53; 33419-42-0/Etoposide; 7722-84-1/Hydrogen Peroxide; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

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


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