title: Inhibitor of apoptosis proteins as intracellular signaling intermediates.
abstract: Inhibitor of apoptosis (IAP) proteins have often been considered inhibitors of cell death due to early reports that described their ability to directly bind and inhibit caspases, the primary factors that implement apoptosis. However, a greater understanding is evolving regarding the vital roles played by IAPs as transduction intermediates in a diverse set of signaling cascades associated with functions ranging from the innate immune response to cell migration to cell-cycle regulation. In this review, we discuss the functions of IAPs in signaling, focusing primarily on the cellular IAP (c-IAP) proteins. The c-IAPs are important components in tumor necrosis factor receptor superfamily signaling cascades, which include activation of the NF-κB transcription factor family. As these receptors modulate cell proliferation and cell death, the involvement of the c-IAPs in these pathways provides an additional means of controlling cellular fate beyond simply inhibiting caspase activity. Additionally, IAP-binding proteins, such as Smac and caspases, which have been described as having cell death-independent roles, may affect c-IAP activity in intracellular signaling. Collectively, the multi-faceted functions and complex regulation of the c-IAPs illustrate their importance as intracellular signaling intermediates.
authors.affiliation: Graduate Program in Immunology, The University of Michigan, Ann Arbor, MI, USA.|Department of Pathology, The University of Michigan, Ann Arbor, MI, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Kocab
authors.affiliation: Department of Pathology, The University of Michigan, Ann Arbor, MI, USA.|Department of Internal Medicine, The University of Michigan, Ann Arbor, MI, USA.
authors.forename: Colin S
authors.initials: CS
authors.lastname: Duckett
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D020169:Caspases / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D018716:Molecular Mimicry; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015398:Signal Transduction; D054852:Small Molecule Libraries / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D018124:Receptors, Tumor Necrosis Factor; D054852:Small Molecule Libraries; D020169:Caspases
keywords: NF-κB; Smac; Smac mimetic; apoptosis; caspases; cd30; cell signaling; inhibitor of apoptosis protein (IAP); tumor necrosis factor (TNF); ubiquitin-mediated signaling