BCL-2 FAMILY - REGULATORS OF CELL-DEATH

An expanding family of BCL-2 related proteins share homology, clustere d 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-X-L, BCL-2, and BAX can for m ion-conductive pores in artificial membranes. The BCL-2 family, comp rised of both pro-apoptotic and anti-apoptotic members, acts as a chec kpoint 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- X-L display a reciprocal pattern of expression during lymphocyte devel opment. Gain-and loss-of-function models revealed stage-specific roles for BCL-2 and BCL-X-L. 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 prolif eration and cell death.