title: The Drosophila caspase DRONC cleaves following glutamate or aspartate and is regulated by DIAP1, HID, and GRIM.
abstract: The caspase family of cysteine proteases plays important roles in bringing about apoptotic cell death. All caspases studied to date cleave substrates COOH-terminal to an aspartate. Here we show that the Drosophila caspase DRONC cleaves COOH-terminal to glutamate as well as aspartate. DRONC autoprocesses itself following a glutamate residue, but processes a second caspase, drICE, following an aspartate. DRONC prefers tetrapeptide substrates in which aliphatic amino acids are present at the P2 position, and the P1 residue can be either aspartate or glutamate. Expression of a dominant negative form of DRONC blocks cell death induced by the Drosophila cell death activators reaper, hid, and grim, and DRONC overexpression in flies promotes cell death. Furthermore, the Drosophila cell death inhibitor DIAP1 inhibits DRONC activity in yeast, and DIAP1's ability to inhibit DRONC-dependent yeast cell death is suppressed by HID and GRIM. These observations suggest that DRONC acts to promote cell death. However, DRONC activity is not suppressed by the caspase inhibitor and cell death suppressor baculovirus p35. We discuss possible models for DRONC function as a cell death inhibitor.
authors.affiliation: Division of Biology, MC 156-29, Pasadena, California 91125, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Hawkins
authors.forename: S J
authors.initials: SJ
authors.lastname: Yoo
authors.forename: E P
authors.initials: EP
authors.lastname: Peterson
authors.forename: S L
authors.initials: SL
authors.lastname: Wang
authors.forename: S Y
authors.initials: SY
authors.lastname: Vernooy
authors.forename: B A
authors.initials: BA
authors.lastname: Hay
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D001224:Aspartic Acid / Q000378:metabolism*; D020169:Caspases / Q000737:chemistry / Q000378:metabolism*; D004330:Drosophila / Q000201:enzymology*; D029721:Drosophila Proteins; D018698:Glutamic Acid / Q000378:metabolism*; D006868:Hydrolysis; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D009479:Neuropeptides; C108881:grim protein, Drosophila; D001224:Aspartic Acid; D018698:Glutamic Acid; D020169:Caspases; C118731:dronc protein, Drosophila