STKs catalyse the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K14 (also known as NIK) phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of NF-kB proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others []. NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription [, , ].
TNF receptor-associated factor 1 (TRAF1) plays a role in the regulation of cell survival and apoptosis []. TRAF1 is unique among TRAF proteins in that it lacks a RING domain found in the N-terminal regions of other TRAFs []. The heterotrimer formed by TRAF1 and TRAF2 is part of a E3 ubiquitin-protein ligase complex that promotes ubiquitination of target proteins, such as MAP3K14 [, ].TRAF1 is unique among the TRAFs in that it lacks a RING domain, which is critical for the activation of nuclear factor-kappaB and Jun NH2-terminal kinase. Studies on TRAF1-deficient mice suggest that TRAF1 has a negative regulatory role in TNFR-mediated signaling events []. TRAF1 contains one zinc finger and one TRAF domain.The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded β-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors [, ].
TNF receptor-associated factor 1 (TRAF1) plays a role in the regulation of cell survival and apoptosis []. TRAF1 is unique among TRAF proteins in that it lacks a RING domain found in the N-terminal regions of other TRAFs []. The heterotrimer formed by TRAF1 and TRAF2 is part of a E3 ubiquitin-protein ligase complex that promotes ubiquitination of target proteins, such as MAP3K14 [, ].TRAF1 is unique among the TRAFs in that it lacks a RING domain, which is critical for the activation of nuclear factor-kappaB and Jun NH2-terminal kinase. Studies on TRAF1-deficient mice suggest that TRAF1 has a negative regulatory role in TNFR-mediated signaling events []. TRAF1 contains one zinc finger and one TRAF domain.
