bcl-2 family protein

Introduction

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:
  • cytokine deprivation
  • 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:
  • TNF-receptor
  • CD95

Notes

A hypothesis 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.

More general terms

• bcl protein (B-cell leukemia/lymphoma protein)

More specific terms

• bax subfamily protein
• bcl-2 subfamily protein
• BH3 subfamily protein

Additional terms

• 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)