The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Proapoptotic Bak is sequestered by Mcl-1 and Bcl-x L , but not Bcl-2, until displaced by BH3-only proteins
Open accessAbstract
Commitment of cells to apoptosis is governed largely by the interaction between members of the Bcl-2 protein family. Its three subfamilies have distinct roles: The BH3-only proteins trigger apoptosis by binding via their BH3 domain to prosurvival relatives, while the proapoptotic Bax and Bak have an essential downstream role involving permeabilization of organellar membranes and induction of caspase activation. We have investigated the regulation of Bak and find that, in healthy cells, Bak associates with Mcl-1 and Bcl-x L but surprisingly not Bcl-2, Bcl-w, or A1. These interactions require the Bak BH3 domain, which is also necessary for Bak dimerization and killing activity. When cytotoxic signals activate BH3-only proteins that can engage both Mcl-1 and Bcl-x L (such as Noxa plus Bad), Bak is displaced and induces cell death. Accordingly, the BH3-only protein Noxa could bind to Mcl-1, displace Bak, and promote Mcl-1 degradation, but Bak-mediated cell death also required neutralization of Bcl-x L by other BH3-only proteins. The results indicate that Bak is held in check solely by Mcl-1 and Bcl-x L and induces apoptosis only if freed from both. The finding that different prosurvival proteins have selective roles has notable implications for the design of anti-cancer drugs that target the Bcl-2 family.
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Cites
Danial, N. N., & Korsmeyer, S. J. (2004) · Cell · doi:10.1016/s0092-8674(04)00046-7 · Cited by 4,651
Noxa, a BH3-Only Member of the Bcl-2 Family and Candidate Mediator of p53-Induced Apoptosis
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Mcl-1 deficiency results in peri-implantation embryonic lethality
Rinkenberger, J. L., Horning, S., Klocke, B., Roth, K., & Korsmeyer, S. J. (2000) · Genes & Development · doi:10.1101/gad.14.1.23 · Cited by 397
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Mitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598
Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy
Czabotar, P. E., Lessene, G., Strasser, A., & Adams, J. M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3722 · Cited by 3,219
Self-citationMitochondria 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
Programmed Anuclear Cell Death Delimits Platelet Life Span
Mason, K. D., Carpinelli, M. R., Fletcher, J. I., Collinge, J. E., Hilton, A. A., Ellis, S., Kelly, P. N., Ekert, P. G., Metcalf, D., Roberts, A. W., et al. (2007) · Cell · doi:10.1016/j.cell.2007.01.037 · Cited by 1,031
Self-citationMaurer, U., Charvet, C., Wagman, A. S., Dejardin, E., & Green, D. R. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.02.009 · Cited by 881
Metadata
- Authors
- Willis, S. N., Chen, L., Dewson, G., Wei, A., Naik, E., Fletcher, J. I., Adams, J. M., & Huang, D. C. S.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-05-18
- Volume
- 19
- Issue
- 11
- Pages
- 1294-1305
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2166467949
- Cited by
- 1,233
- References
- 5
- Type
- posted content
- Language
- en
- Open access
- diamond
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