cIAP1/2 participates in positive and negative regulation of NF-κB. cIAP1/2 are recruited to an activated TNF receptor where they mediate K-63 polyubiquitination of RIP1. RIP1 subsequently activates the IKK complex, resulting in activation of canonical NF-κB complexes. In contrast, cIAP1/2 represses activation of canonical and noncanonical NF-κB signaling by ubiquitinating NIK, leading to its degradation. Mutation or loss of cIAP1/2 results in accumulation of NIK, resulting in activation of both canonical and noncanonical NF-κB. Activated NF-κB complexes promote the transcription of various growth and survival factors, such as IL6 (Interleukin 6) and BAFF (B-cell activating factor). cIAP, cellular inhibitor of apoptosis; IKK, IκB kinase; NIK, NF-κB inducing kinase; RIP, receptor interacting protein; TNF, tumour necrosis factor; TNFR, TNF receptor; TRAF, TNFR-associated factor; TRADD, TNFR-associated death domain.