BRCA1 regulates the interferon gamma-mediated apoptotic response

Paul Harkin, D.A. Haber, Patrick Johnston, H.N. Andrews, Paul Mullan, S. McWilliams, S. Sebelova, J. O'Brien, P.M. Gilmore, N. McCabe, A. Pace, B. Koller

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

Abstract

BRCA1 is a tumor suppressor gene implicated in transcriptional regulation. We have generated cell lines with inducible expression of BRCA1 as a tool to identify downstream targets that may be important mediators of BRCA1 function. Oligonucleotide array-based expression profiling identified 11 previously described interferon regulated genes that were up-regulated following inducible expression of BRCA1. Northern blot analysis revealed that a subset of the identified targets including IRF-7, MxA, and ISG-54 were synergistically up-regulated by BRCA1 in the presence of interferon gamma (IFN-gamma) but not interferons alpha or beta. Importantly, IFN-gamma-mediated induction of IRF-7 and MxA was attenuated in the BRCA1 mutant cell line HCC1937, an effect that was rescued following reconstitution of exogenous wild type BRCA1 in these cells. Furthermore, reconstituted BRCA1 sensitized HCC1937 cells to IFN-gamma-induced apoptotic cell death. This study identifies BRCA1 as a component of the IFN-gamma-regulated signaling pathway and suggests that BRCA1 may play a role in the regulation of IFN-gamma-mediated apoptosis.

Original languageEnglish
Pages (from-to)26225-26232
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number29
DOIs
Publication statusPublished - 19 Jul 2002

ASJC Scopus subject areas

  • Biochemistry

Fingerprint

Dive into the research topics of 'BRCA1 regulates the interferon gamma-mediated apoptotic response'. Together they form a unique fingerprint.

Cite this