期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 290, 期 11, 页码 7304-7313出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.611186
关键词
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资金
- National Institutes of Health [GM081685, DE014756]
- Department of Obstetrics and Gynecology, University of Texas Medical Branch (Galveston, TX)
- Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston (Houston, TX)
- Cancer Institute of New South Wales, Australia [12/CDF/2-12]
- Pennsylvania Department of Health
The inositol 1,4,5-trisphosphate receptor (IP3R) is a ubiquitously expressed endoplasmic reticulum (ER)-resident calcium channel. Calcium release mediated by IP(3)Rs influences many signaling pathways, including those regulating apoptosis. IP3R activity is regulated by protein-protein interactions, including binding to proto-oncogenes and tumor suppressors to regulate cell death. Here we show that the IP3R binds to the tumor suppressor BRCA1. BRCA1 binding directly sensitizes the IP3R to its ligand, IP3. BRCA1 is recruited to the ER during apoptosis in an IP3R-dependent manner, and, in addition, a pool of BRCA1 protein is constitutively associated with the ER under non-apoptotic conditions. This is likely mediated by a novel lipid binding activity of the first BRCA1 C terminus domain of BRCA1 These findings provide a mechanistic explanation by which BRCA1 can act as a proapoptotic protein.
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