title: The p35 relative, p49, inhibits mammalian and Drosophila caspases including DRONC and protects against apoptosis.
abstract: This study characterized the ability of a new member of the p35 family, p49, to inhibit a number of mammalian and insect caspases. p49 blocked apoptosis triggered by treatment with Fas ligand (FasL), Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or ultraviolet (UV) radiation but provided negligible protection against apoptosis induced by the chemotherapeutic drug cisplatin. The caspase cleavage site in p49 was determined, and mutation of the P1 residue of this site abolished the ability of p49 to inhibit caspases, implying that p49 inhibits caspases through an analogous suicide-substrate mechanism to p35. Unlike p35, p49 inhibited the upstream insect caspase DRONC.
authors.affiliation: Department of Haematology and Oncology, Royal Children's Hospital, Parkville 3052, Australia.
authors.forename: A M
authors.initials: AM
authors.lastname: Jabbour
authors.forename: P G
authors.initials: PG
authors.lastname: Ekert
authors.forename: E J
authors.initials: EJ
authors.lastname: Coulson
authors.forename: M J
authors.initials: MJ
authors.lastname: Knight
authors.forename: D M
authors.initials: DM
authors.lastname: Ashley
authors.forename: C J
authors.initials: CJ
authors.lastname: Hawkins
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D005057:Eukaryotic Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D053222:Fas Ligand Protein; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D012441:Saccharomyces cerevisiae; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D053221:TNF-Related Apoptosis-Inducing Ligand; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014466:Ultraviolet Rays; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D061945:Caspase Inhibitors; D029721:Drosophila Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; C117171:P49 protein, Spodoptera littoralis nucleopolyhedrovirus; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; C081618:p35 protein, Nucleopolyhedrovirus; D020169:Caspases; C118731:dronc protein, Drosophila; D002945:Cisplatin