title: Understanding IAP function and regulation: a view from Drosophila.
abstract: Apoptosis is an active form of cell suicide that results in the orderly death and phagocytosis of cells during normal development and in the adult. Many death signals lead to the activation of members of a family of cysteine proteases known as caspases. These proteins act to transduce death signals from different cellular compartments and they cleave a number of cellular proteins, leading ultimately to many of the biochemical and morphological events associated with death. Many mechanisms act to inhibit cell death upstream of caspase activation. However, only one family of cellular proteins, the inhibitors of apoptosis (IAPs), has been identified that inhibit caspase activation and/or activity. The observations that IAP function is essential for cell survival in Drosophila, and that IAP expression is deregulated in many forms of cancer in humans, argue that IAPs are important cell death inhibitors and that deregulation of their function is likely to be important in human disease. Here we review IAP function, with particular reference to insights that study of the Drosophila IAPs has provided. We also discuss some directions for future study.
authors.affiliation: Division of Biology, MC 156-29, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA. haybruce@its.caltech.edu
authors.forename: B A
authors.initials: BA
authors.lastname: Hay
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000502:physiology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D009479:Neuropeptides / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D014452:Ubiquitins / Q000378:metabolism
chemical_list: C107489:BIRC5 protein, human; D001426:Bacterial Proteins; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009479:Neuropeptides; D010455:Peptides; D011506:Proteins; D000077022:Survivin; D014452:Ubiquitins; C108881:grim protein, Drosophila; C086973:rpr protein, Drosophila; D020169:Caspases