title: Gcn2 mediates Gcn4 activation in response to glucose stimulation or UV radiation not via GCN4 translation.
abstract: In mammalian cells transcription factors of the AP-1 family are activated by either stress signals such as UV radiation, or mitogenic signals such as growth factors. Here we show that a similar situation exists in the yeast Saccharomyces cerevisiae. The AP-1 transcriptional activator Gcn4, known to be activated by stress signals such as UV radiation and amino acids starvation, is also induced by growth stimulation such as glucose. We show that glucose-dependent Gcn4 activation is mediated through the Ras/cAMP pathway. This pathway is also responsible for UV-dependent Gcn4 activation but is not involved in Gcn4 activation by amino acid starvation. Thus, the unusual phenomenon of activation of mitogenic pathways and AP-1 factors by contradictory stimuli through Ras is conserved from yeast to mammals. We also show that activation of Gcn4 by glucose and UV requires Gcn2 activity. However, in contrast to its role in amino acid starvation, Gcn2 does not increase eIF2alpha phosphorylation or translation of GCN4 mRNA in response to glucose or UV. These findings suggest a novel mechanism of action for Gcn2. The finding that Gcn4 is activated in response to glucose via the Ras/cAMP pathway suggests that this cascade coordinates glucose metabolism with amino acids and purine biosynthesis and thereby ensures availability of both energy and essential building blocks for continuation of the cell cycle.
authors.affiliation: Department of Biological Chemistry, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Marbach
authors.forename: R
authors.initials: R
authors.lastname: Licht
authors.forename: H
authors.initials: H
authors.lastname: Frohnmeyer
authors.forename: D
authors.initials: D
authors.lastname: Engelberg
mesh_terms: D000429:Alcohol Oxidoreductases; D000596:Amino Acids / Q000378:metabolism; D000619:Aminohydrolases; D000242:Cyclic AMP / Q000502:physiology; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011755:Pyrophosphatases; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism* / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D014466:Ultraviolet Rays; D001616:beta-Galactosidase / Q000235:genetics; D020703:ras GTPase-Activating Proteins / Q000502:physiology
chemical_list: D000596:Amino Acids; D004268:DNA-Binding Proteins; D015852:Eukaryotic Initiation Factor-2; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D020703:ras GTPase-Activating Proteins; D000242:Cyclic AMP; D000429:Alcohol Oxidoreductases; C092116:HIS4 protein, S cerevisiae; D011494:Protein Kinases; C512912:GCN2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D001616:beta-Galactosidase; D000619:Aminohydrolases; D011755:Pyrophosphatases; D005947:Glucose