title: Crosstalk between the Tor and Gcn2 pathways in response to different stresses.
abstract: Regulating growth and the cell cycle in response to environmental fluctuations is important for all organisms in order to maintain viability. Two major pathways for translational regulation are found in higher eukaryotes: the Tor signaling pathway and those operating through the eIF2α kinases. Studies from several organisms indicate that the two pathways are interlinked, in that Tor complex 1 (TORC1) negatively regulates the Gcn2 kinase. Furthermore, inactivation of TORC1 may be required for activation of Gcn2 in response to stress. Here, we use the model organism Schizosaccharomyces pombe to investigate this crosstalk further. We find that the relationship is more complex than previously thought. First, in response to UV irradiation and oxidative stress, Gcn2 is fully activated in the presence of TORC1 signaling. Second, during amino-acid starvation, activation of Gcn2 is dependent on Tor2 activity, and Gcn2 is required for timely inactivation of the Tor pathway. Our data show that the crosstalk between the two pathways varies with the actual stress applied.
authors.affiliation: Department of Cell Biology; Institute for Cancer Research; Oslo University Hospital; Oslo, Norway.
authors.forename: Gro Elise
authors.initials: GE
authors.lastname: Rødland
authors.affiliation: Department of Cell Biology; Institute for Cancer Research; Oslo University Hospital; Oslo, Norway.
authors.forename: Tonje
authors.initials: T
authors.lastname: Tvegård
authors.affiliation: Department of Cell Biology; Institute for Cancer Research; Oslo University Hospital; Oslo, Norway; Institute for Molecular Biosciences; University of Oslo; Oslo, Norway.
authors.forename: Erik
authors.initials: E
authors.lastname: Boye
authors.affiliation: Department of Cell Biology; Institute for Cancer Research; Oslo University Hospital; Oslo, Norway.
authors.forename: Beáta
authors.initials: B
authors.lastname: Grallert
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D013217:Starvation / Q000378:metabolism*; D013312:Stress, Physiological; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D000596:Amino Acids; D015852:Eukaryotic Initiation Factor-2; D029702:Schizosaccharomyces pombe Proteins; C539007:Gcn2 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: Gcn2; S. pombe; Tor; UV irradiation; oxidative stress; starvation