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Two modes of action of anti-apoptotic BCL-2 proteins. Anti-apoptotic BCL-2 proteins can prevent apoptosis either by binding to BH3-only direct activator proteins (MODE 1) or by binding to active BAX or BAK (MODE 2). Additional BH3-only protein interactions can neutralize the function of the anti-apoptotic BCL-2 protein, allowing apoptosis to proceed. MODE 1 is more readily derepressed than MODE 2 (i.e., MODE 2 is functionally more stable).
