In mammals, there are five members: BCL-2 itself, BCL-XL, BCL-W, MCL-1 and BFL-1. The last faction within the BCL-2 family are the “BCL-2-like” pro-survival proteins. A consequence of this event is the release of apoptogenic factors such as cytochrome c from the mitochondria into the cytosol, leading to activation of the cellular demolitionists, the caspases. These multi-domain proteins, once activated, oligomerise to form pores resulting in mitochondrial outer membrane permeabilisation. This family which includes BAX, BAK and BOK are the downstream effectors of the family. The second sub-family of death-promoting molecules are the “BAX/BAK-like” proteins. In mammals, there are eight main members including BIM, PUMA, BID, NOXA, BID, BAD, BMF and HRK. Upon receipt of a death stimulus, these BH3-only proteins are transcriptionally upregulated, or post-translationally modified, enabling them to act on downstream pro- and anti-apoptotic family members, thereby initiating the slippery slide to cell death. The first comprise the “BH3-only” proteins which trigger the apoptotic cascade. Of the cell death promoters, there are two sub-families. Within the BCL-2 family, there are proteins that promote cell death and others that enable cell survival. These events lead to BAX/BAK oligomerization followed by mitochondrial outer membrane permeabilisation, caspase activation and death. The BH3-only proteins trigger the apoptotic cascade by either binding the BCL-2-like pro-survival proteins, displacing the BAX/BAK-like proteins, or alternatively in the case of certain members (e.g., BIM, BID, PUMA), by directly engaging and activating BAX/BAK.
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