title: Dredd, a novel effector of the apoptosis activators reaper, grim, and hid in Drosophila.
abstract: Caspases are widely conserved proteases considered to be essential effectors of apoptosis. We identified a novel Drosophila gene, dredd, which shares extensive homology to all members of the caspase gene family. Cells specified for programmed death in development exhibit a striking accumulation of dredd RNA that requires signaling by the death activators REAPER, GRIM, and HID. Furthermore, directed misexpression of each activator was sufficient to drive ectopic accumulation of dredd RNA. Heterozygosity at the dredd locus suppressed apoptosis in transgenic models of reaper- and grim-induced cell killing, demonstrating that levels of dredd product can modulate signaling triggered by these death activators. Finally, expression of REAPER, GRIM, and HID was found to trigger processing of DREDD protein precursor through a mechanism that is insensitive to, and upstream of, known caspase inhibitors. Taken together, these observations establish mechanistic connections between activators of apoptosis and a new downstream death effector in Drosophila.
authors.affiliation: Department of Cell Biology and Neuroscience, University of Texas, Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9039, USA.
authors.forename: P
authors.initials: P
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Rodriguez
authors.forename: R
authors.initials: R
authors.lastname: Erskine
authors.forename: T
authors.initials: T
authors.lastname: Thach
authors.forename: J M
authors.initials: JM
authors.lastname: Abrams
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000737:chemistry*; D003001:Cloning, Molecular; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins; D005786:Gene Expression Regulation / Q000235:genetics; D017403:In Situ Hybridization; D019476:Insect Proteins / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009479:Neuropeptides / Q000502:physiology*; D010455:Peptides / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013489:Suppression, Genetic / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D019476:Insect Proteins; D009479:Neuropeptides; D010455:Peptides; D012333:RNA, Messenger; C108881:grim protein, Drosophila; C086973:rpr protein, Drosophila; D020169:Caspases