The Bcl-2 family of proteins contains at least 15 members which can have pro-or anti-apoptotic effects. All share at least one of four Bcl-2 homology domains (BH1 to BH4), and inclusion of different BH domains in individual Bcl-2 family members is generally responsible for pro-or anti-apoptotic activity (reviewed in1). Pro-and anti-apoptotic members can form heterodimers, and their ratio may determine whether a death or survival signal is delivered. 2 There is strong evidence that the actions of Bcl-2 proteins are exerted at the level of the mitochondrial membrane (reviewed in3). Thus many Bcl-2 members are anchored in the mitochondrial outer membrane, and anti-apoptotic family members such as Bcl-2 and Bcl-xL form ion channels which increase the rate of proton extrusion from mitochondria.

Some studies have begun to address the transcriptional regulation of anti-apoptotic Bcl-2 genes. In leukaemias, for example, a hybrid transcription factor formed by chromosomal rearrangement increases Bcl-2 expression, 4 and overexpression of the CCAAT enhancer binding protein, GADD153, reduces Bcl-2 expression with an accompany-