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
The versatility and universality of calcium signalling
Berridge, M. J., Lipp, P., & Bootman, M. D. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35036035 · Cited by 5,701
Self-citationMitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598
Shimizu, S., Narita, M., Tsujimoto, Y., & Tsujimoto, Y. (1999) · Nature · doi:10.1038/20959 · Cited by 2,178
Kuwana, T., Bouchier-Hayes, L., Chipuk, J. E., Bonzon, C., Sullivan, B. A., Green, D. R., & Newmeyer, D. D. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.02.003 · Cited by 1,185
Mitochondrial apoptosis without VDAC
Galluzzi, L., & Kroemer, G. (2007) · Nature Cell Biology · doi:10.1038/ncb0507-487 · Cited by 91
Cited by
Mitochondria as sensors and regulators of calcium signalling
Rizzuto, R., De Stefani, D., Raffaello, A., & Mammucari, C. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3412 · Cited by 1,781
Mechanisms of Action of Bcl-2 Family Proteins
Shamas-Din, A., Kale, J., Leber, B., & Andrews, D. W. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008714 · Cited by 705
The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy
Vogler, M., Braun, Y., Smith, V. M., Westhoff, M.-A., Pereira, R. S., Pieper, N. M., Anders, M., Callens, M., Vervliet, T., Abbas, M., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02176-0 · Cited by 462
Self-citationBCL-2 family: integrating stress responses at the ER to control cell demise
Pihán, P., Carreras-Sureda, A., & Hetz, C. (2017) · Cell Death & Differentiation · doi:10.1038/cdd.2017.82 · Cited by 274
Marchi, S., Giorgi, C., Galluzzi, L., & Pinton, P. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.04.017 · Cited by 235
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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