Apoptotic Proteins

Apoptotic proteins play a vital role in maintaining homeostasis in an organism. Their function is closely related to their subcellular location. The Bcl-2 family proteins function in a distal apoptotic pathway and have either pro-apoptotic or anti-apoptotic effects. For example, Bid (Bcl-2 interacting Domain), belongs to a subset of pro-apoptotic regulators that is cleaved and activated by caspase-8, which facilitates its translocation to the mitochondria. Bcl-10 promotes apoptosis through interactions with cIAPs (cellular inhibitors of apoptosis). Fas ligands induce apoptosis by binding to Fas. Activation of Fas results in the recruitment of FADD (Fas-associated protein with death domain) that subsequently results in the activation of caspase-8. TRAIL (Tumor necrosis related apoptosis-inducing ligand) promotes apoptosis by its interaction with death receptors DR4 and DR5 in a wide variety of tumor cells. PARP (Poly(ADP-ribose) polymerase), a multi-functional enzyme, is an important contributor to genetic stability, but is actively cleaved by caspases during apoptosis.  Smac/DIABLO (Second mitochondria-derived activator of caspase/direct IAP-binding protein with low pI), a100 kDa mitochondrial protein, potentiates apoptosis by neutralizing one or more members of the IAP family of apoptosis inhibitory proteins. Although apoptotic proteins have a wide degree of heterogeneity, they all function in a coordinated manner under the influence of apoptotic death signals.