BCL-xL (BCL2L1)
BCL-xL is an anti-apoptotic member of the BCL-2 family that restrains mitochondrial outer-membrane permeabilization by binding pro-apoptotic family members.
Function
BCL-xL is embedded in the mitochondrial outer membrane, where it binds the pore-formers BAX and BAK and the BH3-only activators that activate them. Its binding groove is also the target of the BH3-only “sensitizer” proteins, so the amount of free BAX and BAK depends on the balance of these family members. The BCL2L1 gene is spliced into two main products: BCL-xL, the long anti-apoptotic form, and BCL-xS, a shorter pro-apoptotic form.
In cancer
BCL-xL is overexpressed in many carcinomas and in platelets, where it keeps anucleate cells alive; this platelet dependence explains the thrombocytopenia that limits drugs targeting BCL-xL. Tumors use BCL-xL to survive chemotherapy, and its expression correlates with resistance to taxanes and other agents. Because BCL-2, BCL-xL and MCL-1 each protect against partially overlapping sets of death signals, tumors often shift dependence among the three as treatment selects for resistant clones.
Notes
- Human gene symbol: BCL2L1; UniProt Q07817; 233 amino acids (long isoform); BH1-BH4 domains and a C-terminal membrane anchor.