title: A cooperative role for Atf1 and Pap1 in the detoxification of the oxidative stress induced by glucose deprivation in Schizosaccharomyces pombe.
abstract: In Schizosaccharomyces pombe, glucose concentrations below a certain threshold trigger the stress-activated protein kinase (SAPK) signal transduction pathway and promote increased transcription of Atf1-dependent genes coding for the general stress response. Removal of glucose specifically induces the nuclear accumulation of green fluorescent protein-labeled Pap1 (GFP-Pap1) and the expression of genes dependent on this transcription factor. In contrast, depletion of the nitrogen source triggers the SAPK pathway but does not activate Pap1-dependent gene transcription, indicating that carbon stress rather than growth arrest leads to an endogenous oxidative condition that favors nuclear accumulation of Pap1. The reductant agents glutathione or N-acetylcysteine suppress the nuclear accumulation of GFP-Pap1 induced by glucose deprivation without inhibiting the activation of the MAPK Sty1. In addition, cells expressing a mutant GFP-Pap1 unable to accumulate into the nucleus upon hydrogen peroxide-mediated oxidative stress failed to show this protein into the nucleus in the absence of glucose. These results support the concept of a concerted action between the SAPK pathway and the Pap1 transcription factor during glucose exhaustion by which glucose limitation induces activation of the SAPK pathway prior to the oxidative stress caused by glucose deprivation. The ensuing induction of Atf1-dependent genes (catalase) decreases the level of hydroperoxides allowing Pap1 nuclear accumulation and function. Congruent with this interpretation, glucose-depleted cells show higher adaptive response to exogenous oxidative stress than those maintained in the presence of glucose.
authors.affiliation: Department of Genetics and Microbiology, Facultad de Biología, University of Murcia, 30071 Murcia, Spain.
authors.forename: Marisa
authors.initials: M
authors.lastname: Madrid
authors.forename: Teresa
authors.initials: T
authors.lastname: Soto
authors.forename: Alejandro
authors.initials: A
authors.lastname: Franco
authors.forename: Vanessa
authors.initials: V
authors.lastname: Paredes
authors.forename: Jero
authors.initials: J
authors.lastname: Vicente
authors.forename: Elena
authors.initials: E
authors.lastname: Hidalgo
authors.forename: Mariano
authors.initials: M
authors.lastname: Gacto
authors.forename: José
authors.initials: J
authors.lastname: Cansado
mesh_terms: D051697:Activating Transcription Factor 1; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins / Q000502:physiology*; D005656:Fungal Proteins / Q000502:physiology*; D005947:Glucose / Q000172:deficiency*; D008658:Inactivation, Metabolic; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics*; D000073718:Pancreatitis-Associated Proteins; D010750:Phosphoproteins / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000502:physiology*; D015398:Signal Transduction; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D051697:Activating Transcription Factor 1; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D000073718:Pancreatitis-Associated Proteins; C105096:Pap1 protein, S pombe; D010750:Phosphoproteins; C000612141:REG3A protein, human; D029702:Schizosaccharomyces pombe Proteins; C106740:atf1 protein, S pombe; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose