(A) The antiapoptotic proteins (eg, BCL-2, BCL-XL, BCL-W, MCL-1) are prosurvival proteins that bind the proapoptotic multidomain effectors BAK and BAX to prevent cell death, promoting cell survival. (B) A variety of cell stressors increase the expression of the proapoptotic sensors, including the BH3-only proteins (ie, BIM, BID, PUMA, NOXA, and BAD). (C) The BH3-only proteins subsequently displace or prevent the antiapoptotic proteins from binding to BAX and BAK, leading to cytochrome c release into the cytosol and activation of the caspase cascade, resulting in cell death. BCL-2=B-cell lymphoma–2; BH3=BCL-2 homology 3; MCL-1=myeloid cell leukemia sequence 1.