What question did this study set out to answer?

Investigate how the tumor suppressor protein BRCA1 interacts with inositol 1,4,5-trisphosphate receptors to modulate endoplasmic reticulum calcium signaling and promote apoptosis.

February 3, 2015Journal of Biological ChemistryOpen Access

The BRCA1 Tumor Suppressor Binds to Inositol 1,4,5-Trisphosphate Receptors to Stimulate Apoptotic Calcium Release

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Authors

SHSerena Clark HedgepethThe University of Texas Medical Branch at Galveston MGM. Iveth GarciaUnited States Food and Drug Administration LWLarry E. WagnerUniversity of Rochester Medical Center

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Implication

Mechanistic study demonstrates that BRCA1 enhances endoplasmic reticulum calcium release via direct IP3 receptor binding, highlighting a novel proapoptotic pathway.

Key Points

Investigate how the tumor suppressor protein BRCA1 interacts with inositol 1,4,5-trisphosphate receptors to modulate endoplasmic reticulum calcium signaling and promote apoptosis.
Evaluated direct protein-protein binding interactions between BRCA1 and the endoplasmic reticulum-resident calcium channel IP3R.
Assessed IP3R sensitivity and calcium release in response to IP3 in the presence of BRCA1.
Analyzed the subcellular localization and lipid-binding properties of the BRCA1 C-terminus domain under basal and apoptotic conditions.
BRCA1 directly interacts with IP3R and sensitizes the channel to its activating ligand, IP3.
BRCA1 is recruited to the endoplasmic reticulum during apoptosis in an IP3R-dependent manner, with a resident pool constitutively bound under non-apoptotic conditions.
Constitutive endoplasmic reticulum binding is driven by an uncharacterized lipid-binding activity located in the first BRCA1 C-terminus domain, mechanistically linking BRCA1 to apoptotic calcium induction.

Cite This Study

Hedgepeth et al. (2015) studied this question.

synapsesocial.com/papers/69d89044c025a7c015bee223 https://doi.org/10.1074/jbc.m114.611186

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Implication

Mechanistic study demonstrates that BRCA1 enhances endoplasmic reticulum calcium release via direct IP3 receptor binding, highlighting a novel proapoptotic pathway.

The BRCA1 Tumor Suppressor Binds to Inositol 1,4,5-Trisphosphate Receptors to Stimulate Apoptotic Calcium Release

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Implication

Key Points

Cite This Study

The BRCA1 Tumor Suppressor Binds to Inositol 1,4,5-Trisphosphate Receptors to Stimulate Apoptotic Calcium Release

Discussion

Member takes

Implication

Key Points

Cite This Study

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