Roles of c-IAP proteins in TNF receptor family activation of NF-κB signaling.
Precise regulation of survival and signaling pathways is essential for proper maintenance of organismal homeostasis, development, and immune defense. Inhibitor of apoptosis (IAP) proteins are evolutionarily conserved regulators of cell death and immune signaling that impact numerous cellular processes. Initially characterized as inhibitors of apoptosis, the ubiquitin ligase activity of IAP proteins is critical for modulating various signaling pathways (e.g., NF-κB, MAPK) and cellular fate. Cellular IAP1 and IAP2 regulate the pro-survival canonical NF-κB pathway by ubiquitinating RIP1 and enabling recruitment of kinase (IKK) and E3 ligase (LUBAC) complexes. On the other hand, c-IAP1 and c-IAP2 are negative regulators of noncanonical NF-κB signaling by promoting ubiquitination and consequent degradation of the NF-κB-inducing kinase NIK. In this article, we describe the involvement of c-IAP1 and c-IAP2 in NF-κB signaling and provide detailed methodology for examining how c-IAPs exert their functional roles.
Department of Early Discovery Biochemistry, Genentech, Inc., South San Francisco, CA, 94080, USA.
Eugene
E
Varfolomeev
Tatiana
T
Goncharov
Domagoj
D
Vucic
D015153:Blotting, Western / Q000379:methods; D002460:Cell Line; D004789:Enzyme Activation; D015870:Gene Expression; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008024:Ligands; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction; D013347:Subcellular Fractions; D014162:Transfection
D051034:Inhibitor of Apoptosis Proteins; D008024:Ligands; D016328:NF-kappa B; D034741:RNA, Small Interfering; D018124:Receptors, Tumor Necrosis Factor; D020928:Mitogen-Activated Protein Kinases