The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
The BH4 domain of Bcl-2 inhibits ER calcium release and apoptosis by binding the regulatory and coupling domain of the IP3 receptor
Open accessAbstract
Although the presence of a BH4 domain distinguishes the antiapoptotic protein Bcl-2 from its proapoptotic relatives, little is known about its function. BH4 deletion converts Bcl-2 into a proapoptotic protein, whereas a TAT-BH4 fusion peptide inhibits apoptosis and improves survival in models of disease due to accelerated apoptosis. Thus, the BH4 domain has antiapoptotic activity independent of full-length Bcl-2. Here we report that the BH4 domain mediates interaction of Bcl-2 with the inositol 1,4,5-trisphosphate (IP3) receptor, an IP3-gated Ca 2+ channel on the endoplasmic reticulum (ER). BH4 peptide binds to the regulatory and coupling domain of the IP3 receptor and inhibits IP3-dependent channel opening, Ca 2+ release from the ER, and Ca 2+ -mediated apoptosis. A peptide inhibitor of Bcl-2-IP3 receptor interaction prevents these BH4-mediated effects. By inhibiting proapoptotic Ca 2+ signals at their point of origin, the Bcl-2 BH4 domain has the facility to block diverse pathways through which Ca 2+ induces apoptosis.
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Cites
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Mitochondria as sensors and regulators of calcium signalling
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Mechanisms of Action of Bcl-2 Family Proteins
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The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy
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Metadata
- Authors
- Rong, Y.-P., Bultynck, G., Aromolaran, A. S., Zhong, F., Parys, J. B., De Smedt, H., Mignery, G. A., Roderick, H. L., Bootman, M. D., & Distelhorst, C. W.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-08-25
- Volume
- 106
- Issue
- 34
- Pages
- 14397-14402
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2011931042
- Cited by
- 307
- References
- 5
- FWCI
- 6.84
- Type
- journal article
- Language
- en
- Open access
- green
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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