RRC ID 9561
Author Hayakawa T, Kato K, Hayakawa R, Hisamoto N, Matsumoto K, Takeda K, Ichijo H.
Title Regulation of anoxic death in Caenorhabditis elegans by mammalian apoptosis signal-regulating kinase (ASK) family proteins.
Journal Genetics
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.
Volume 187(3)
Pages 785-92
Published 2011-3-1
DOI 10.1534/genetics.110.124883
PII genetics.110.124883
PMID 21212236
PMC PMC3063672
MeSH Animals Apoptosis* Apoptosis Regulatory Proteins Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology Cell Hypoxia / genetics Cytoskeletal Proteins / genetics Cytoskeletal Proteins / physiology Insulin / genetics Insulin / physiology MAP Kinase Kinase 4 / genetics MAP Kinase Kinase 4 / physiology MAP Kinase Kinase Kinase 5 / genetics MAP Kinase Kinase Kinase 5 / physiology* Mitogen-Activated Protein Kinases / genetics Mutation Protein-Serine-Threonine Kinases / genetics Protein-Serine-Threonine Kinases / physiology Receptors, G-Protein-Coupled Signal Transduction / genetics
IF 4.015
Times Cited 26
C.elegans tm850 tm3036