The transgenic mice bearing NIKΔT3 mutant develop B-cell hyperplasia, severe autoimmune disorders and tumors in multiple organs.275 Although TRAF3 is identified as the negative regulator of NIK, TRAF3 does not catalyze ubiquitination of NIK in vitro, suggesting TRAF3 may function as the adaptor protein rather than direct ubiquitin E3 ligase.276 Study has identified cIAP1 and cIAP2 as E3 ubiquitin ligases that mediate NIK ubiquitination.276 Indeed, TRAF2/3 and cIAP1/2 form a complex, in which TRAF2 serves as a linker to connect TRAF3 to cIAP1/2 since TRAF3 does not bind cIAPs directly. The gene discussed is MAP3K14; the disease is autoimmune disease.