BCL-2
BCL-2 is a mitochondrial outer-membrane protein that prevents apoptosis by binding and neutralizing the pro-apoptotic members of its own family.
Function
BCL-2 sits on the mitochondrial outer membrane and holds the pore-forming proteins BAX and BAK inactive, either by sequestering them directly or through the BH3-only intermediary proteins that report cellular stress. When stress dominates, BH3-only proteins displace BCL-2, BAX and BAK oligomerize, the mitochondrial outer membrane permeabilizes, cytochrome c escapes into the cytosol, and APAF1 assembles the apoptosome. The BCL-2 family therefore sets the threshold at which a cell commits to apoptosis.
In cancer
The BCL2 gene earned its name at the chromosomal breakpoint of follicular lymphoma, where translocation places it under the control of a constitutive immunoglobulin promoter and the protein accumulates. Lymphocytes that should die survive, and the lymphoma grows from that refusal. Overexpression of BCL-2 contributes to many cancers, which made the protein a drug target: venetoclax, a BH3-mimetic that occupies the same binding groove as the natural BH3-only proteins, is approved for chronic lymphocytic leukemia.