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bcl-2 family protein

A family of proteins containing at least one of four highly conserved regions, bc1-2 homology domains (BH1 - BH4 domains). Function: - some promote cell survival (bcl-2, bcl-xL, bcl-w, mcl-1, A1) - others promote apoptosis [bax, bak, bok/mtd, bcl-xS, bad, bid, bik/nbk, bim, hrk] - Bcl-2 subfamily proteins promote cell survival - Bax subfamily proteins & BH3 subfamily proteins tend to promote apoptosis - the bcl-2 family of proteins regulates cellular response to diverse cytotoxic conditions including: a) cytokine deprivation b) DNA damage (probably exclusively double-strand breaks) from radiation & drugs - they have little impact on the signal from death receptors that activate caspase-8 through FADD/Mort1: a) TNF-receptor b) CD95 Notes: A hypothesis [2] has been put forth that bcl-2 family members regulate mitochondrial membrane permeability through interaction with each other & with VDAC-1. Closure of the VDAC-1 channel is the earliest observed mitochondrial change during apoptosis blocking passage of ADT/ATP. It is thought that bcl-2 may stabilize the open conformation of VDAC-1. When a death signal has recruited a BH3 subfamily protein to the mitochondria, their interaction with a bcl-2 subfamily protein might close the VDAC-1 channel. The ensuing ionic & pH changes could initiate trans- location & oligomerization of bax subfamily proteins which, renders VDAC-1 & ANT of the permeability transition pore complex (PTPC) permeable to cytochrome c. Cytosolic cytochrome c then activates APAF-1 & caspase-9 to initiate apoptosis.

Related

apoptosis apoptotic protease-activating factor 1; APAF-1 (APAF1, KIAA0413) caspase-9; ice-like apoptotic protease 6; ICE-LAP6; apoptotic protease MCH-6 (CASP9, MCH6) cytochrome c (CYCS) mitochondrial permeability transition pore complex (PTPC) voltage-dependent anion-selective channel protein 1; VDAC-1; hVDAC1; outer mitochondrial membrane protein porin 1; plasmalemmal porin; porin 31HL; porin 31HM (VDAC1 VDAC)

Specific

bax subfamily protein bcl-2 subfamily protein BH3 subfamily protein

General

bcl protein (B-cell leukemia/lymphoma protein)

Properties

MOTIF: BH domain NAME: BH domain

References

  1. Bernardi P, Petronilli V, Di Lisa F, Forte M. A mitochondrial perspective on cell death. Trends Biochem Sci. 2001 Feb;26(2):112-7. Review. PMID: 11166569
  2. Adams JM, Cory S. Life-or-death decisions by the Bcl-2 protein family. Trends Biochem Sci. 2001 Jan;26(1):61-6. Review. PMID: 11165519
  3. Antonsson B, Martinou JC. The Bcl-2 protein family. Exp Cell Res. 2000 Apr 10;256(1):50-7. Review. PMID: 10739651