Document Detail


Nuclear export of BRCA1 occurs during early S phase and is calcium-dependent.
MedLine Citation:
PMID:  18296025     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although the breast cancer susceptibility gene 1 (BRCA1) protein is predominantly nuclear, its localization can vary during the cell cycle in response to cellular insults. For example, in S-phase cells, BRCA1 forms subnuclear foci and localizes to the perinuclear region in response to DNA damage. The present study provides evidence that BRCA1 is transiently excluded from the nucleus during the early part of S phase in the absence of DNA damage. The percentage of MCF-7 human breast cancer cells predominantly expressing nonnuclear BRCA1 significantly correlates with the percentage of cells within early S phase. This redistribution of BRCA1 is partially sensitive to leptomycin B, indicating that CRM-1-mediated nuclear export is involved. Similar results were observed with MCF-12A nonmalignant human mammary cells. The abilities of BAPTA-AM, an intracellular calcium chelator, to inhibit the change in BRCA1 localization, and of A23187, a calcium ionophore, and of thapsigargin to mimic nuclear exclusion of BRCA1, provide evidence for the involvement of calcium in this process. The calcium-mediated change in BRCA1 localization occurs in several cell lines, indicating that this effect is not cell line specific. BRCA2 localization is not affected by A23187. Furthermore, inhibition of calcium-calmodulin interaction and calcium-calmodulin dependent protein kinase II attenuates the calcium-mediated change in BRCA1 localization. These data suggest that BRCA1 nuclear export can be cell cycle-regulated by a calcium-dependent mechanism.
Authors:
Katherine Glover-Collins; Marilyn E Thompson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-01-19
Journal Detail:
Title:  Cellular signalling     Volume:  20     ISSN:  0898-6568     ISO Abbreviation:  Cell. Signal.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-03-07     Completed Date:  2008-05-23     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  8904683     Medline TA:  Cell Signal     Country:  England    
Other Details:
Languages:  eng     Pagination:  958-68     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Active Transport, Cell Nucleus / drug effects
Apoptosis Regulatory Proteins
BRCA1 Protein / metabolism*
BRCA2 Protein / metabolism
Breast / cytology,  metabolism
Breast Neoplasms / metabolism*,  pathology
Calcimycin / pharmacology
Calcium / metabolism*
Calcium Signaling / drug effects
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
Cell Line, Tumor
Egtazic Acid / analogs & derivatives,  pharmacology
Epithelial Cells / cytology,  drug effects,  metabolism
Fatty Acids, Unsaturated / pharmacology
Female
Humans
S Phase
Signal Transduction / drug effects
Grant Support
ID/Acronym/Agency:
2G12RR03032/RR/NCRR NIH HHS; CA68485/CA/NCI NIH HHS; DK20593/DK/NIDDK NIH HHS; DK58404/DK/NIDDK NIH HHS; K01 CA089494-05/CA/NCI NIH HHS; K01 CA89494/CA/NCI NIH HHS; T32 GM007347/GM/NIGMS NIH HHS; T32 GM007347-25/GM/NIGMS NIH HHS; T32 GM07347/GM/NIGMS NIH HHS; U54 CA091408-05/CA/NCI NIH HHS; U54 CA91408/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/BLID protein, human; 0/BRCA1 Protein; 0/BRCA1 protein, human; 0/BRCA2 Protein; 0/BRCA2 protein, human; 0/Fatty Acids, Unsaturated; 139890-68-9/1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; 37H9VM9WZL/Calcimycin; 526U7A2651/Egtazic Acid; 87081-35-4/leptomycin B; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinase Type 2; SY7Q814VUP/Calcium
Comments/Corrections

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


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