Gene interactions and pathways from curated databases and text-mining
Mol Cancer Res 2007, PMID: 17374731

BRCA1 regulates IFN-gamma signaling through a mechanism involving the type I IFNs.

Buckley, Niamh E; Hosey, Alison M; Gorski, Julia J; Purcell, James W; Mulligan, Jude M; Harkin, D Paul; Mullan, Paul B

BRCA1 encodes a tumor suppressor gene that is mutated in the germ line of women with a genetic predisposition to breast and ovarian cancer. BRCA1 has been implicated in a number of important cellular functions including DNA damage repair, transcriptional regulation, cell cycle control, and ubiquitination. Using an Affymetrix U95A microarray, IRF-7 was identified as a BRCA1 transcriptional target and was also shown to be synergistically up-regulated by BRCA1 specifically in the presence of IFN-gamma, coincident with the synergistic induction of apoptosis. We show that BRCA1, signal transducer and activator of transcription (STAT)-1, and STAT2 are all required for the induction of IRF-7 following stimulation with IFN-gamma. We also show that the induction of IRF-7 by BRCA1 and IFN-gamma is dependent on the type I IFNs, IFN-alpha and IFN-beta. We show that BRCA1 is required for the up-regulation of STAT1, STAT2, and the type I IFNs in response to IFN-gamma. We show that BRCA1 is localized at the promoters of the molecules involved in type I IFN signaling leading to their up-regulation. Blocking this intermediary type I IFN step using specific antisera shows the requirement for IFN-alpha and IFN-beta in the induction of IRF-7 and apoptosis. Finally, we outline a mechanism for the BRCA1/IFN-gamma regulation of target genes involved in the innate immune response, which is dependent on type I IFN signaling.

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Text Mining Data

IFN-gamma → BRCA1: " BRCA1 regulates IFN-gamma signaling through a mechanism involving the type I IFNs "

BRCA1 → IFN-gamma: " Using an Affymetrix U95A microarray, IRF-7 was identified as a BRCA1 transcriptional target and was also shown to be synergistically up-regulated by BRCA1 specifically in the presence of IFN-gamma , coincident with the synergistic induction of apoptosis "

IRF-7 → BRCA1: " Using an Affymetrix U95A microarray, IRF-7 was identified as a BRCA1 transcriptional target and was also shown to be synergistically up-regulated by BRCA1 specifically in the presence of IFN-gamma, coincident with the synergistic induction of apoptosis "

IRF-7 → IFN-gamma: " Using an Affymetrix U95A microarray, IRF-7 was identified as a BRCA1 transcriptional target and was also shown to be synergistically up-regulated by BRCA1 specifically in the presence of IFN-gamma , coincident with the synergistic induction of apoptosis "

IRF-7 → BRCA1: " We show that BRCA1 , signal transducer and activator of transcription ( STAT ) -1, and STAT2 are all required for the induction of IRF-7 following stimulation with IFN-gamma "

IRF-7 → STAT2: " We show that BRCA1, signal transducer and activator of transcription ( STAT ) -1, and STAT2 are all required for the induction of IRF-7 following stimulation with IFN-gamma "

IRF-7 → BRCA1: " We also show that the induction of IRF-7 by BRCA1 and IFN-gamma is dependent on the type I IFNs, IFN-alpha and IFN-beta "

IRF-7 → IFN-gamma: " We also show that the induction of IRF-7 by BRCA1 and IFN-gamma is dependent on the type I IFNs, IFN-alpha and IFN-beta "

STAT1 → BRCA1: " We show that BRCA1 is required for the up-regulation of STAT1 , STAT2, and the type I IFNs in response to IFN-gamma "

STAT1 → IFN-gamma: " We show that BRCA1 is required for the up-regulation of STAT1 , STAT2, and the type I IFNs in response to IFN-gamma "

STAT2 → BRCA1: " We show that BRCA1 is required for the up-regulation of STAT1, STAT2 , and the type I IFNs in response to IFN-gamma "

STAT2 → IFN-gamma: " We show that BRCA1 is required for the up-regulation of STAT1, STAT2 , and the type I IFNs in response to IFN-gamma "

IRF-7 → IFN-beta: " Blocking this intermediary type I IFN step using specific antisera shows the requirement for IFN-alpha and IFN-beta in the induction of IRF-7 and apoptosis "

Manually curated Databases

  • IRef Innatedb Interaction: IFNA1 — BRCA1 (unknown, -)
  • IRef Innatedb Interaction: BRCA1 — IFNB1 (unknown, -)
In total, 2 gene pairs are associated to this article in curated databases