NIK (E5S4V) Rabbit mAb #86473

Transcription factors of the nuclear factor κB (NF-κB)/Rel family play a pivotal role in inflammatory and immune responses (1,2). There are five family members in mammals: Rel-A, c-Rel, Rel-B, NF-κB1 (p105/p50), and NF-κB2 (p100/p52). p105 and p100 are proteolytically processed by the proteasome to produce p50 and p52, respectively. The p50 and p52 products form dimeric complexes with Rel proteins, which are then able to bind DNA and regulate transcription. In unstimulated cells, NF-κB is sequestered in the cytoplasm by its inhibitory proteins, the IκBs (3-5). NF-κB-activating agents can induce the phosphorylation of IκBs, which targets them for rapid degradation through a ubiquitin-proteasome pathway, releasing NF-κB to enter the nucleus and regulate gene expression (6-8). Processing of NF-κB2 is regulated by IKK1 (IKKα), which triggers the phosphorylation and processing to p52, which can then undergo nuclear translocation (9-11).

Activation of NF-κB can be controlled by NF-kB-inducing kinase (NIK), a member of the MAP3K family that was originally identified as a TRAF2-interacting protein and thereby coupled to receptor activation (12). NIK forms a complex with and phosphorylates IKK1 and IKK2, subsequently leading to the phosphorylation of IκB and translocation of NF-κB to the nucleus (13-15).