BRCA1 Regulates the Interferon γ-mediated Apoptotic Response
| Autor: | Daniel A. Haber, Nuala McCabe, Amy J. Pace, Paul B. Mullan, Heather N. Andrews, Stewart McWilliams, Patrick G. Johnston, Beverly H. Koller, D. Paul Harkin, Jennifer E. Quinn, Paula M. Gilmore, Šárka Šebelová |
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| Rok vydání: | 2002 |
| Předmět: |
Myxovirus Resistance Proteins
endocrine system diseases Tumor suppressor gene Interferon Regulatory Factor-7 Blotting Western Genes BRCA1 Apoptosis Biology Biochemistry Cell Line Interferon-gamma GTP-Binding Proteins Interferon medicine Transcriptional regulation Humans Interferon gamma Northern blot skin and connective tissue diseases Molecular Biology Oligonucleotide Array Sequence Analysis Regulation of gene expression BRCA1 Protein Cell Biology Up-Regulation Cell biology DNA-Binding Proteins Gene Expression Regulation Protein Biosynthesis Cancer research Signal transduction medicine.drug Interferon regulatory factors |
| Zdroj: | Journal of Biological Chemistry. 277:26225-26232 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m201316200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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