Localization of BRCA1 and a splice variant identifies the nuclear localization signal

Sanjay Thakur, Hong Bing Zhang, Yi Peng, Huy Le, Bryan Carroll, Theresa Ward, Jie Yao, Linda M. Farid, Fergus J. Couch, Robert B. Wilson, Barbara L. Weber

Research output: Contribution to journalArticle

215 Scopus citations

Abstract

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 BRCA1Δ672-4095. Immunofluorescence studies indicate nuclear localization of BRCA1 but cytoplasmic localization of BRCA1Δ672-4095. 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.

Original languageEnglish (US)
Pages (from-to)444-452
Number of pages9
JournalMolecular and cellular biology
Volume17
Issue number1
DOIs
StatePublished - Jan 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Thakur, S., Zhang, H. B., Peng, Y., Le, H., Carroll, B., Ward, T., Yao, J., Farid, L. M., Couch, F. J., Wilson, R. B., & Weber, B. L. (1997). Localization of BRCA1 and a splice variant identifies the nuclear localization signal. Molecular and cellular biology, 17(1), 444-452. https://doi.org/10.1128/MCB.17.1.444