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Conversion of Bcl-2 to a Bax-like Death Effector by Caspases
Abstract
Caspases are a family of cysteine proteases implicated in the biochemical and morphological changes that occur during apoptosis (programmed cell death). The loop domain of Bcl-2 is cleaved at Asp 34 by caspase-3 (CPP32) in vitro, in cells overexpressing caspase-3, and after induction of apoptosis by Fas ligation and interleukin-3 withdrawal. The carboxyl-terminal Bcl-2 cleavage product triggered cell death and accelerated Sindbis virus–induced apoptosis, which was dependent on the BH3 homology and transmembrane domains of Bcl-2. Inhibitor studies indicated that cleavage of Bcl-2 may further activate downstream caspases and contribute to amplification of the caspase cascade. Cleavage-resistant mutants of Bcl-2 had increased protection from interleukin-3 withdrawal and Sindbis virus–induced apoptosis. Thus, cleavage of Bcl-2 by caspases may ensure the inevitability of cell death.
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Citations
Cited by
Cleavage of BID by Caspase 8 Mediates the Mitochondrial Damage in the Fas Pathway of Apoptosis
Li, H., Zhu, H., Xu, C.-J., & Yuan, J. (1998) · Cell · doi:10.1016/s0092-8674(00)81590-1 · Cited by 4,445
Mitochondria and cell death: outer membrane permeabilization and beyond
Tait, S. W. G., & Green, D. R. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2952 · Cited by 2,593
(2001) · PubMed · Cited by 2,381
Intrinsically disordered protein
Dunker, A. K., Lawson, J. D., Brown, C. J., Williams, R. M., Romero, P., Oh, J. S., Oldfield, C. J., Campen, A. M., Ratliff, C. M., Hipps, K. W., et al. (2001) · Journal of Molecular Graphics and Modelling · doi:10.1016/s1093-3263(00)00138-8 · Cited by 2,272
Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes
Shimizu, S., Kanaseki, T., Mizushima, N., Mizuta, T., Arakawa-Kobayashi, S., Thompson, C. B., & Tsujimoto, Y. (2004) · Nature Cell Biology · doi:10.1038/ncb1192 · Cited by 1,358
Metadata
- Authors
- Cheng, E. H.-Y., Kirsch, D. G., Clem, R. J., Ravi, R., Kastan, M. B., Bedi, A., Ueno, K., & Hardwick, J. M.
- Venue
- Science
- Published
- 1997-12-12
- Volume
- 278
- Issue
- 5345
- Pages
- 1966-1968
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2092759765
- Cited by
- 1,107
- References
- 0
- FWCI
- 33.64
- Type
- journal article
- Language
- en
- Open access
- closed
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- Cheng, E. H.-Y., Kirsch, D. G., Clem, R. J., Ravi, R., Kastan, M. B., Bedi, A., Ueno, K., & Hardwick, J. M. (1997). Conversion of Bcl-2 to a Bax-like Death Effector by Caspases. Science. https://doi.org/10.1126/science.278.5345.1966
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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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