title: Regulation of anoxic death in Caenorhabditis elegans by mammalian apoptosis signal-regulating kinase (ASK) family proteins.
abstract: Cells and organisms face anoxia in a wide variety of contexts, including ischemia and hibernation. Cells respond to anoxic conditions through multiple signaling pathways. We report that NSY-1, the Caenorhabditis elegans ortholog of mammalian apoptosis signal-regulating kinase (ASK) family of MAP kinase (MAPK) kinase kinases (MAP3Ks), regulates viability of animals in anoxia. Loss-of-function mutations of nsy-1 increased survival under anoxic conditions, and increased survival was also observed in animals with mutations in tir-1 and the MAPK kinase (MAP2K) sek-1, which are upstream and downstream factors of NSY-1, respectively. Consistent with these findings, anoxia was found to activate the p38 MAPK ortholog PMK-1, and this was suppressed in nsy-1 and tir-1 mutant animals. Furthermore, double-mutant analysis showed that the insulin-signaling pathway, which also regulates viability in anoxia, functioned in parallel to NSY-1. These results suggest that the TIR-1-NSY-1-SEK-1-PMK-1 pathway plays important roles in the reponse to anoxia in C. elegans.
authors.affiliation: Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, Strategic Approach to Drug Discovery and Development in Pharmaceutical Sciences, Global Center of Excellence Program, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan.
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Hayakawa
authors.forename: Kumiko
authors.initials: K
authors.lastname: Kato
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Hayakawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Hisamoto
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Takeda
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ichijo
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology; D015687:Cell Hypoxia / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology; D007328:Insulin / Q000235:genetics / Q000502:physiology; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000502:physiology; D048848:MAP Kinase Kinase Kinase 5 / Q000235:genetics / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; C485906:tir-1 protein, C elegans; C532433:NSY-1 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; C463460:Pmk-1 protein, C elegans; D048848:MAP Kinase Kinase Kinase 5; D048670:MAP Kinase Kinase 4; C516679:sek-1 protein, C elegans