BRCA1 Regulates IFN-γ Signaling through a Mechanism Involving the Type I IFNs
Data(s) |
01/03/2007
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Resumo |
<p>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.</p> |
Identificador |
http://dx.doi.org/10.1158/1541-7786.MCR-06-0250 http://www.scopus.com/inward/record.url?scp=34147114266&partnerID=8YFLogxK |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Buckley , N , Hosey , A M , Gorski , J J , Purcell , J W , Mulligan , J M , Harkin , D P & Mullan , P B 2007 , ' BRCA1 Regulates IFN-γ Signaling through a Mechanism Involving the Type I IFNs ' Molecular Cancer Research , vol 5 , no. 3 , pp. 261-270 . DOI: 10.1158/1541-7786.MCR-06-0250 |
Palavras-Chave | #/dk/atira/pure/subjectarea/asjc/1300/1306 #Cancer Research #/dk/atira/pure/subjectarea/asjc/1300/1312 #Molecular Biology |
Tipo |
article |