Mammalian IAP proteins comprise eight family members, including X chromosome-linked IAP (XIAP), cellular IAP1 (cIAP1), and cIAP2. Among other functions, XIAP can antagonize apoptosis by inhibiting caspases. cIAP proteins act as E3 ubiquitin ligases that mediate ubiquitination of target proteins via their really interesting new gene (RING) domain. Human cancers typically express high levels of IAP proteins which favor their evasion of programmed cell death. Endogenous Smac protein promotes cell death upon its release from the mitochondrial intermembrane space into the cytosol by antagonizing IAP proteins.IAP proteins are their integral components that activate NF-kB and mitogen-activated protein kinase (MAPK) pathways upon ubiquitin chain scaffolds.  In TNF family, stimulated signaling E3 ligases c-IAP1 and c-IAP2 are recruited through the adaptor protein TRAF2 to receptor-associated complexes where they promote K63- and K11-linked polyubiquitylation of RIP1, NEMO, TRAF2, and themselves. While cellular IAP proteins are required for the activation of TNF family-induced canonical NF-kB signaling, they are negative regulators of the noncanonical NF-kB pathway. IAP proteins may also play a role in DNA damage, Wnt signaling, cell motility and migration, and autophagy pathways.


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