XIAP

By Rachel M.A. Linger, Ph.D.

In the first installment of this two-part blog post titled "Apoptosis and Necroptosis: Important factors to identify both types of programmed cell death", the mechanisms by which cell death occurs and ways to identify these pathways were discussed. In this next segment, we focus on the molecular factors regulating the choice between programmed cell death and survival signaling.

Caspases are essential mediators of programmed cell death and are needed for both the induction of apoptosis as well as for aiding the degradation of cellular structures. Initiator caspases (such as Caspase-9) sense and respond to various signals including intracellular stress or binding of the death receptor to external ligands. Upon dimerization, initiator caspases gets activated, which follows cleavage of downstream effector caspases for carrying out the apoptotic program.

The inhibitor of apoptosis proteins (IAPs) are important regulators of cell death and inflammation. The cellular inhibitor of apoptosis protein 2 (cIAP2) contains three Baculovirus IAP repeat (BIR) domains, a Ubiquitin associated (UBA) domain, and a RING domain with E3 ligase activity. cIAP2 inhibits apoptosis through direct inhibition of the pro-apoptotic caspase-3. cIAP2 also regulates cell survival through its role in the tumor necrosis factor alpha (TNF-alpha) signaling pathway.