Document Detail


Localization of BRCA1 and a splice variant identifies the nuclear localization signal.
MedLine Citation:
PMID:  8972225     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Inherited mutations in BRCA1 confer susceptibility to breast and ovarian neoplasms. However, the function of BRCA1 and the role of BRCA1 in noninherited cancer remain unknown. Characterization of alternately spliced forms of BRCA1 may identify functional regions; thus, we constructed expression vectors of BRCA1 and a splice variant lacking exon 11, designated BRCA1 delta 672-4095. Immunofluorescence studies indicate nuclear localization of BRCA1 but cytoplasmic localization of BRCA1 delta 672-4095. Two putative nuclear localization signals (designated NLS1 and NLS2) were identified in exon 11; immunofluorescence studies indicate that only NLS1 is required for nuclear localization. RNA analysis indicates the expression of multiple, tissue-specific forms of BRCA1 RNAs; protein analysis with multiple antibodies suggests that at least three BRCA1 isoforms are expressed, including those lacking exon 11. The results suggest that BRCA1 is a nuclear protein and raise the possibility that splicing is one form of regulation of BRCA1 function by alteration of the subcellular localization of expressed proteins.
Authors:
S Thakur; H B Zhang; Y Peng; H Le; B Carroll; T Ward; J Yao; L M Farid; F J Couch; R B Wilson; B L Weber
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  17     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1997 Jan 
Date Detail:
Created Date:  1997-01-22     Completed Date:  1997-01-22     Revised Date:  2010-09-13    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  444-52     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
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MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Alternative Splicing*
Animals
BRCA1 Protein / analysis*,  chemistry,  genetics
COS Cells
Cell Nucleus / chemistry*
Cytoplasm / chemistry
DNA, Complementary / genetics
Exons / genetics
Genes, BRCA1 / genetics*
Humans
Mice
Molecular Weight
RNA, Messenger / analysis
Sequence Deletion
Grant Support
ID/Acronym/Agency:
CA61231/CA/NCI NIH HHS; CA67403/CA/NCI NIH HHS; K08 HL02871/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/BRCA1 Protein; 0/DNA, Complementary; 0/RNA, Messenger
Comments/Corrections

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