title: IAP family of cell death and signaling regulators.
abstract: Inhibitor of apoptosis (IAP) proteins interface with, and regulate a large number of, cell signaling pathways. If there is a common theme to these pathways, it is that they are involved in the development of the immune system, immune responses, and unsurprisingly, given their name, cell death. Beyond that it is difficult to discover an underlying logic because sometimes IAPs are required to inhibit or prevent signaling, whereas in other cases they are required for signaling to take place. In whatever role they play, they are recruited into signaling complexes and function as ubiquitin E3 ligases, via their RING domains. This review discusses IAP regulation of signaling pathways and focuses on the mammalian IAPs, XIAP, c-IAP1, and c-IAP2, with a particular emphasis on techniques and methods that were used to uncover their roles. We also provide a perspective on targeting IAP proteins for therapeutic intervention and methods used to define the clinical relevance of IAP proteins.
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia. Electronic address: silke@wehi.edu.au.
authors: John
authors: J
authors: Silke
authors: Department of Early Discovery Biochemistry, Genentech, Inc., South San Francisco, California, USA. Electronic address: domagoj@gene.com.
authors: Domagoj
authors: D
authors: Vucic
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination / Q000235:genetics; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D051636:X-Linked Inhibitor of Apoptosis Protein; D044767:Ubiquitin-Protein Ligases
keywords: Apoptosis; BIR domain; Cancer; IAP; IAP antagonist; Inhibitor of apoptosis; NF-κB; Necroptosis; RING domain; RIP1; Smac; Smac-mimetic; TNF; TRAF; XIAP; c-IAP