Evidence for a transcriptional activation function of BRCA1 C-terminal region

Alvaro N.A. Monteiro, Avery August, Hidesaburo Hanafusa

Research output: Contribution to journalArticlepeer-review

409 Scopus citations

Abstract

Mutations in BRCA1 account for 45% of families with high incidence of breast cancer and for 80-90% of families with both breast and ovarian cancer. BRCA1 protein includes an amino-terminal zinc finger motif as well as an excess of negatively charged amino acids near the C terminus, in addition, BRCA1 contains two nuclear localization signals and localizes to the nucleus of normal cells. While these features suggest a role in transcriptional regulation, no function has been assigned to BRCA1. Here, we show that the C-terminal region, comprising exons 16-24 (aa 1560-1863) of BRCA1 fused to GAL4 DNA binding domain can activate transcription both in yeast and mammalian cells. Furthermore, we define the region comprising exons 21-24 (aa 1760-1863) as the minimal transactivation domain. Any one of four germ-line mutations in the C-terminal region found in patients with breast or ovarian cancer (Ala-1708 → Glu, Gln-1756 C+, Met-1775 → Arg, Tyr-1853 → Stop), had markedly impaired transcription activity. Together these data underscore the notion thai one of the functions of BRCA1 may be the regulation of transcription.

Original languageEnglish (US)
Pages (from-to)13595-13599
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number24
DOIs
StatePublished - Nov 26 1996

All Science Journal Classification (ASJC) codes

  • General

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