BAK1 (BAK)
BAK (BCL-2 homologous antagonist/killer) is a mitochondrial outer-membrane protein that forms the apoptotic pore together with BAX.
Function
BAK is anchored permanently in the mitochondrial outer membrane in an inactive conformation. Stress-activated BH3-only proteins — BID and BIM in particular — expose the helix that lets BAK oligomerize; the BAK–BAX oligomers permeabilize the outer membrane, releasing cytochrome c into the cytosol and committing the cell to caspase-dependent death. Anti-apoptotic family members (BCL-2, BCL-xL, MCL-1) hold BAK shut, and the MCL-1–BAK pair is a common resistance axis in cancer therapy.
In cancer
Cells lacking both BAX and BAK resist mitochondrial apoptosis almost completely, so the pair controls commitment to the intrinsic pathway. Tumors rarely delete BAK outright; they more often raise the anti-apoptotic proteins that keep it shut, and BH3-mimetic drugs work by prying BAK and BAX free. Viruses encode BAK-binding inhibitors, evidence of how central this step is to the host–pathogen conflict.
Notes
- Human gene symbol: BAK1; UniProt Q16611; 185 amino acids; BH1–BH3 domains and a C-terminal transmembrane anchor.