title: Regulation of Cell Death by IAPs and Their Antagonists.
abstract: Inhibitors of apoptosis (IAPs) family of genes encode baculovirus IAP-repeat domain-containing proteins with antiapoptotic function. These proteins also contain RING or UBC domains and act by binding to major proapoptotic factors and ubiquitylating them. High levels of IAPs inhibit caspase-mediated apoptosis. For these cells to undergo apoptosis, IAP function must be neutralized by IAP-antagonists. Mammalian IAP knockouts do not exhibit obvious developmental phenotypes, but the cells are more sensitized to apoptosis in response to injury. Loss of the mammalian IAP-antagonist ARTS results in reduced stem cell apoptosis. In addition to the antiapoptotic properties, IAPs regulate the innate immune response, and the loss of IAP function in humans is associated with immunodeficiency. The roles of IAPs in Drosophila apoptosis regulation are more apparent, where the loss of IAP1, or the expression of IAP-antagonists in Drosophila cells, is sufficient to trigger apoptosis. In this organism, apoptosis as a fate is conferred by the transcriptional induction of the IAP-antagonists. Many signaling pathways often converge on shared enhancer regions of IAP-antagonists. Cell death sensitivity is further regulated by posttranscriptional mechanisms, including those regulated by kinases, miRs, and ubiquitin ligases. These mechanisms are employed to eliminate damaged or virus-infected cells, limit neuroblast (neural stem cell) numbers, generate neuronal diversity, and sculpt tissue morphogenesis.
authors.affiliation: Department of Cell Biology, New York University School of Medicine, New York, New York, USA.
authors.forename: Deepika
authors.initials: D
authors.lastname: Vasudevan
authors.affiliation: Department of Cell Biology, New York University School of Medicine, New York, New York, USA. Electronic address: hyungdon.ryoo@nyumc.org.
authors.forename: Hyung Don
authors.initials: HD
authors.lastname: Ryoo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D016923:Cell Death; D002465:Cell Movement; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D007113:Immunity, Innate / Q000502:physiology; D051034:Inhibitor of Apoptosis Proteins / Q000502:physiology*; D008322:Mammals / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009024:Morphogenesis; D009420:Nervous System / Q000166:cytology / Q000254:growth & development
chemical_list: D051017:Apoptosis Regulatory Proteins; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins
keywords: ARTS; Apoptosis; BRUCE; DIAP1; HID; IAP-antagonist; REAPER; SMAC; XIAP; c-IAP1