The BRCA1 Tumor Suppressor Binds to Inositol 1,4,5-Trisphosphate Receptors to Stimulate Apoptotic Calcium Release
| Autor: | David I. Yule, Russell R. Snyder, Damian B. van Rossum, Serena C. Hedgepeth, Larry E. Wagner, Kirsty M. Brodie, Ana M. Rodriguez, M. Iveth Garcia, Sree V. Chintapalli, Beric R. Henderson, Gary D.V. Hankins, Darren Boehning |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Programmed cell death endocrine system diseases chemistry.chemical_element Apoptosis Biology Calcium Endoplasmic Reticulum Biochemistry chemistry.chemical_compound Cell Line Tumor Neoplasms Humans Inositol 1 4 5-Trisphosphate Receptors Inositol Calcium Signaling skin and connective tissue diseases Receptor Molecular Biology BRCA1 Protein Endoplasmic reticulum Calcium channel fungi food and beverages Cell Biology Ligand (biochemistry) Cell biology chemistry Immunology Signal transduction Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 290:7304-7313 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m114.611186 |
| Popis: | The inositol 1,4,5-trisphosphate receptor (IP3R) is a ubiquitously expressed endoplasmic reticulum (ER)-resident calcium channel. Calcium release mediated by IP3Rs 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. |
| Databáze: | OpenAIRE |
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