How the Bcl-2 family of proteins interact to regulate apoptosis - PubMed (original) (raw)
Review
How the Bcl-2 family of proteins interact to regulate apoptosis
Mark F van Delft et al. Cell Res. 2006 Feb.
Abstract
Commitment of cells to apoptosis is governed largely by protein-protein interactions between members of the Bcl-2 protein family. Its three sub-families have distinct roles: the BH3-only proteins trigger apoptosis by binding via their BH3 domain to pro-survival relatives, while the pro-apoptotic Bax and Bak have an essential downstream role involving disruption of organellar membranes and induction of caspase activation. The BH3-only proteins act as damage sensors, held inert until their activation by stress signals. Once activated, they were thought to bind promiscuously to pro-survival protein targets but unexpected selectivity has recently emerged from analysis of their interactions. Some BH3-only proteins also bind to Bax and Bak. Whether Bax and Bak are activated directly by these BH3-only proteins, or indirectly as a consequence of BH3-only proteins neutralizing their pro-survival targets is the subject of intense debate. Regardless of this, a detailed understanding of the interactions between family members, which are often selective, has notable implications for designing anti-cancer drugs to target the Bcl-2 family.
Similar articles
- Induction of apoptosis in prostate carcinoma cells by BH3 peptides which inhibit Bak/Bcl-2 interactions.
Finnegan NM, Curtin JF, Prevost G, Morgan B, Cotter TG. Finnegan NM, et al. Br J Cancer. 2001 Jul 6;85(1):115-21. doi: 10.1054/bjoc.2001.1850. Br J Cancer. 2001. PMID: 11437412 Free PMC article. - Triggering of apoptosis by Puma is determined by the threshold set by prosurvival Bcl-2 family proteins.
Callus BA, Moujallad DM, Silke J, Gerl R, Jabbour AM, Ekert PG, Vaux DL. Callus BA, et al. J Mol Biol. 2008 Dec 12;384(2):313-23. doi: 10.1016/j.jmb.2008.09.041. Epub 2008 Sep 25. J Mol Biol. 2008. PMID: 18835564 - A putative role for human BFK in DNA damage-induced apoptosis.
Ozören N, Inohara N, Núñez G. Ozören N, et al. Biotechnol J. 2009 Jul;4(7):1046-54. doi: 10.1002/biot.200900091. Biotechnol J. 2009. PMID: 19557800 - Bcl-2 family proteins: the sentinels of the mitochondrial apoptosis pathway.
Wong WW, Puthalakath H. Wong WW, et al. IUBMB Life. 2008 Jun;60(6):390-7. doi: 10.1002/iub.51. IUBMB Life. 2008. PMID: 18425793 Review. - BH3-only proteins trigger cytochrome c release, but how?
Häcker G, Weber A. Häcker G, et al. Arch Biochem Biophys. 2007 Jun 15;462(2):150-5. doi: 10.1016/j.abb.2006.12.022. Epub 2007 Jan 9. Arch Biochem Biophys. 2007. PMID: 17306210 Review.
Cited by
- Kynurenic acid protects against ischemia/reperfusion injury by modulating apoptosis in cardiomyocytes.
Gáspár R, Nógrádi-Halmi D, Demján V, Diószegi P, Igaz N, Vincze A, Pipicz M, Kiricsi M, Vécsei L, Csont T. Gáspár R, et al. Apoptosis. 2024 Oct;29(9-10):1483-1498. doi: 10.1007/s10495-024-02004-w. Epub 2024 Aug 17. Apoptosis. 2024. PMID: 39153038 Free PMC article. - HPLC-ESI/MS-MS characterization of compounds in Dolomiaea costus extract and evaluation of cytotoxic and antiviral properties: molecular mechanisms underlying apoptosis-inducing effect on breast cancer.
El-Nashar HAS, Eldahshan OA, Fattah NFA, Loutfy SA, Abdel-Salam IM. El-Nashar HAS, et al. BMC Complement Med Ther. 2023 Oct 6;23(1):354. doi: 10.1186/s12906-023-04164-9. BMC Complement Med Ther. 2023. PMID: 37803435 Free PMC article. - Involvement of Both Extrinsic and Intrinsic Apoptotic Pathways in Tridecylpyrrolidine-Diol Derivative-Induced Apoptosis In Vitro.
Nosalova N, Keselakova A, Kello M, Martinkova M, Fabianova D, Pilatova MB. Nosalova N, et al. Int J Mol Sci. 2023 Jul 20;24(14):11696. doi: 10.3390/ijms241411696. Int J Mol Sci. 2023. PMID: 37511455 Free PMC article. - UvATG6 Interacts with BAX Inhibitor 1 Proteins and Plays Critical Roles in Growth, Conidiation, and Virulence in Ustilaginoidea virens.
Gu L, Wang Y, Xie S, Liu Y, Yan J, Yin W, Luo C. Gu L, et al. Microbiol Spectr. 2023 Jun 15;11(3):e0489822. doi: 10.1128/spectrum.04898-22. Epub 2023 Apr 27. Microbiol Spectr. 2023. PMID: 37102873 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials