BCL-2 FAMILY: Regulators of Cell Death

An expanding family of BCL-2 related proteins share homology, clustered within four conserved regions, namely BCL-2 homology (BH1-4) domains, which control the ability of these proteins to dimerize and function as regulators of apoptosis. Moreover, BCL-XL, BCL-2, and BAX can form ion-conductive pores in artificial membranes. The BCL-2 family, comprised of both pro-apoptotic and anti-apoptotic members, acts as a checkpoint upstream of CASPASES and mitochondrial dysfunction. BID and BAD possess the minimal death domain BH3, and the phosphorylation of BAD connects proximal survival signals to the BCL-2 family. BCL-2 and BCL-XL display a reciprocal pattern of expression during lymphocyte development. Gain- and loss-of-function models revealed stage-specific roles for BCL-2 and BCL-XL. BCL-2 can rescue maturation at several points of lymphocyte development. The BCL-2 family also reveals evidence for a cell-autonomous coordination between the opposing pathways of proliferation and cell death.