How the Bcl-2 family of proteins interact to regulate apoptosis
- Author(s)
- van Delft, MF; Huang, DC;
- Details
- Publication Year 2006-02,Volume 16,Issue #2,Page 203-213
- Journal Title
- CELL RESEARCH
- Publication Type
- Journal Article
- 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.
- Publisher
- INST BIOCHEMISTRY & CELL BIOLOGY
- Keywords
- MITOCHONDRIAL OUTER-MEMBRANE; CYTOCHROME-C RELEASE; MULTIPLE-MYELOMA CELLS; BH3-ONLY PROTEINS; BH3 DOMAIN; DEFICIENT MICE; IN-VIVO; PERMEABILITY TRANSITION; ENDOPLASMIC-RETICULUM; BAX OLIGOMERIZATION
- Publisher's Version
- https://doi.org/10.1038/sj.cr.7310028
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2006-02-01 12:00:00