Opposing actions of STAT-1 and STAT-3 on the Bcl-2 and Bcl-x promoters

Dear Editor,

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-x_L form ion channels which increase the rate of proton extrusion from mitochondria.

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