Figure 8

Diagram illustrating Bcl-2’s dual antiapoptotic mechanisms and their differential targeting by BIRD-2 and ABT-263. Left, Bcl-2 binds to the IP3Rs, preventing pro-apoptotic Ca2+ elevation. BIRD-2 inhibits this interaction, inducing apoptosis by releasing high levels of Ca2+ from the ER into the cytoplasm. Right, by binding BH3-only proteins such as Bim, Bcl-2 prevents Bim from activating executioner proteins such as Bax/Bak. BH3-mimetic agents such as ABT-263 block this interaction, thereby freeing Bim to trigger apoptosis