title: Metacaspase-8 modulates programmed cell death induced by ultraviolet light and H2O2 in Arabidopsis.
abstract: Programmed cell death (PCD) is a genetically controlled cell death that is regulated during development and activated in response to environmental stresses or pathogen infection. The degree of conservation of PCD across kingdoms and phylum is not yet clear; however, whereas caspases are proteases that act as key components of animal apoptosis, plants have no orthologous caspase sequences in their genomes. The discovery of plant and fungi metacaspases as proteases most closely related to animal caspases led to the hypothesis that metacaspases are the functional homologues of animal caspases in these organisms. Arabidopsis thaliana has nine metacaspase genes, and so far it is unknown which members of the family if any are involved in the regulation of PCD. We show here that metacaspase-8 (AtMC8) is a member of the gene family strongly up-regulated by oxidative stresses caused by UVC, H(2)O(2), or methyl viologen. This up-regulation was dependent of RCD1, a mediator of the oxidative stress response. Recombinant metacaspase-8 cleaved after arginine, had a pH optimum of 8, and complemented the H(2)O(2) no-death phenotype of a yeast metacaspase knock-out. Overexpressing AtMC8 up-regulated PCD induced by UVC or H(2)O(2), and knocking out AtMC8 reduced cell death triggered by UVC and H(2)O(2) in protoplasts. Knock-out seeds and seedlings had an increased tolerance to the herbicide methyl viologen. We suggest that metacaspase-8 is part of an evolutionary conserved PCD pathway activated by oxidative stress.
authors.affiliation: Faculty of Life Sciences, University of Manchester, 3.614 Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom.
authors.forename: Rui
authors.initials: R
authors.lastname: He
authors.forename: Georgina E
authors.initials: GE
authors.lastname: Drury
authors.forename: Vitalie I
authors.initials: VI
authors.lastname: Rotari
authors.forename: Anna
authors.initials: A
authors.lastname: Gordon
authors.forename: Martin
authors.initials: M
authors.lastname: Willer
authors.forename: Tabasum
authors.initials: T
authors.lastname: Farzaneh
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Woltering
authors.forename: Patrick
authors.initials: P
authors.lastname: Gallois
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D017360:Arabidopsis; D029681:Arabidopsis Proteins / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D053181:Caspase 8 / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D016923:Cell Death; D003546:Cysteine Endopeptidases / Q000172:deficiency / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000528:radiation effects; D018506:Gene Expression Regulation, Plant / Q000187:drug effects / Q000528:radiation effects; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D018384:Oxidative Stress; D030821:Plants, Genetically Modified / Q000378:metabolism; D011523:Protoplasts / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014466:Ultraviolet Rays
chemical_list: D029681:Arabidopsis Proteins; D017931:DNA Primers; D006861:Hydrogen Peroxide; D053181:Caspase 8; D003546:Cysteine Endopeptidases; C527345:metacaspase-8, Arabidopsis