BH3-only proteins of the Bcl-2intracellular protein family (BCL2s) , which include Bim, Bmf, Bik, Bad, Bid, Puma, Noxa and Hrk, mediate many developmentally programmed and induced cytotoxic signals.
BH3-only proteins have key roles in development, tissue homeostasis, immunity and tumor suppression, and compounds mimicking them are promising anti-cancer agents.
Their activity is normally constrained by transcriptional and/or diverse post-transcriptional controls.
When activated, these death ligands engage pro-survival Bcl-2-like proteins via the BH3 domain, inactivating their function.
Bim and Puma bind all the pro-survival proteins, whereas others, such as Noxa and Bad, engage distinct subsets and exhibit complementary killing.
Hence, multiple pro-survival proteins must be inactivated to unleash Bax and Bak, which drive apoptosis. Whether certain BH3-only proteins also directly activate Bax/Bak remains controversial.
Members
| BCL2L11 (Bim) | BMF | BIK | BAD | BID | BBC3 (Puma) | PMAIP1 (Noxa) | HRK |
References
Willis SN, Adams JM. Life in the balance: how BH3-only proteins induce apoptosis. Curr Opin Cell Biol. 2005 Dec;17(6):617-25. PMID: 16243507
Gelinas C, White E. BH3-only proteins in control: specificity regulates MCL-1 and BAK-mediated apoptosis. Genes Dev. 2005 Jun 1;19(11):1263-8. PMID: 15937216