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The family: Bcl-2 proteins are split into two broad sub-families, the pro-apoptotic proteins and the anti-apoptotic proteins. The members of this family share characteristic domains of homology entitled the Bcl-2 homology (BH) domains. The BH domains are known to be crucial for function, as deletion of these domains via molecular cloning effects survival/apoptosis rates. The BH domains also serve to further subdivde the pro-apoptotic group into those with several BH domains (e.g. Bax and Bak) or those proteins that have only the BH3 domain (e.g. Bid, Bim and Bad). The Bcl-2 family has a general structure that consists of a hydrophbic helix surrounded by ampipathic helices. Many members of the family have transmembrane domains. The site of action for the Bcl-2 family is mostly on the outer mitochondrial membrane (OMM). Within the mitochondria are apoptogenic factors (cytochrome c, Smac/DIABLO, Omi) that if released activate the executioners of apoptosis, the caspases. Depending on their function, once activated Bcl-2 proteins either promote the release of these factors, or keep them sequestered in the mitochondria. The exact mechanisms surrounding Bcl-2 regulated MMP have yet to be elucidated.
The protein: Bcl-2 is a anti-apoptotic protein that resides in the OMM and the membrane of the endoplasmic reticulum. Over expression of Bcl-2 is known to block cytochrome c release, possibly through the inhibition of Bax and Bak. The protein also conforms to the general structure of Bcl-2 proteins, with a transmembrane domain in its C-terminus.