TRAF2

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.

RANKL (also known as TNF-related activation-induced cytokine), or receptor activator of nuclear factor-κB ligand, was first discovered as a key player in the RANKL/RANK/OPG osteoclast formation pathway.

Despite in depth characterization of the role of IRE1 alpha (inositol-requiring enzyme 1 alpha) in activating the unfolded protein response (UPR) in the ER - little is known about the molecular mechanisms by which this ER protein has shown to regulate intracellular calcium levels and subsequent apoptosis. Intracellular calcium homeostasis is fundamental to many physiological processes, and an increase in Ca2+ is associated with both the early and late stages of apoptosis.

Apoptosis, or programmed cell death, is a normal component of cellular differentiation and the development of multicellular organisms. Receptor activator of NF-kB (RANK) lacks significant homology with the other family members of the tumor necrosis factor receptor (TNFR) superfamily. The cytoplasmic domain of RANK interacts with the tumor necrosis factor receptor associated factors, adaptor proteins such as TRAF2, TRAF5 and TRAF6.