BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program Ren, D. et al. Science 330, 1390–1393 (2010)
The release of cytochrome c from mitochondria is crucial for apoptosis and is regulated by homo-oligomers of the pro-apoptotic proteins BAX and BCL-2 homologous antagonist or killer (BAK). It is not clear how activation of BAX and BAK is controlled, and how BCL-2 homology 3 (BH3)-only proteins of the BCL-2 family are involved in this process. Ren et al. show that the BH3-only proteins BH3-interacting domain death agonist (BID), BCL-2-interacting mediator of cell death (BIM; also known as BCL2L11) and PUMA are essential for homo-oligomerization of BAX and BAK and for the initiation of apoptosis in response to several stimuli. The triple-knockout mice show similar developmental defects to those observed upon loss of BAX and BAK, and cannot respond to death signals despite the presence of other BH3-only factors. Thus, these proteins might directly activate BAX and BAK rather than indirectly act through interactions with anti-apoptotic BCL-2 proteins.
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