Under unstressed cellular conditions these proteins are upregulated in order to bind, interact, and sequester the pro-apoptotic Bax and Bak, preserving the mitochondrial membrane integrity. Anti-apoptotic proteins ( Figure 2B), members of the Bcl-2 family functioning as apoptosis inhibitors, are subclassified into multi BH domain containing Bcl-xL, Bcl-B, Bcl-W, Mcl-1, Bf1 Diva/Boo. Bad (which is induced by nutrition deprivation and growth signals), Smac/Diablo, Hrta/Omi, and Arts are all produced as a result of MOMP. Puma and Noxa which are crucial in cytokines induced apoptosis are produced as a result of DNA damage and transcription of P53. Bcl-2 family either induces apoptosis via multi domain Bax/Bak or inhibits anti-apoptotic proteins (IAPs) belonging to BH3 only family including Puma, Noxa, Bim, Bad, Smac/Diablo, Hrta/Omi, Arts.
Bcl-2 family of proteins is structurally distinguished by the presence of a BH3 domain. Localized to the outer membrane of the mitochondria, it mainly modulates the release of cytochrome c.
(2) Bcl-2 family ( Figure 2B) regulates cells behavior through programmed cell death. There are 14 known proteins belonging to caspases classified according to their structure and function ( Figure 2A). (1) Caspases, aspartate-specific cysteine proteases possess a key role in apoptosis induction and are usually found as inactive heterodimers known as procaspases. Anti-apoptotic proteins are classified as BCL-2 multi-domain proteins (Bcl-xl, Bcl-b, Bcl-w, Mcl-1, Bf1 and DIVA/Boo) and BIR domain family (survivin, livin, bruce, c-IAP and x-IAP). Bcl-2 proteins are classified as multidomain proteins (Bax and Bak) and BH3 only domain that either serve in intermediate pathway (Bid and inhibitors of apoptotic inhibitors such as SMAC/Diablo, HRTA/Omi, Noxa, Puma, Arts and Bim). Caspases are further subdivided according to their role in apoptotic pathway. Pro-apoptotic proteins are classified into Caspases and BCL-2 families. ( B) Classification of apoptotic proteins according to their function in apoptosis. Caspases are divided into three subtypes: inflammatory caspases (1,4,5,11,12,13,14), initiator caspases in intrinsic and extrinsic apoptotic pathways with long N terminal (2,8,9,10), and effector caspases known for their short/absent N-terminal (3,6,7).
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