The glycolytic metabolite methylglyoxal activates Pap1 and Sty1 stress responses in Schizosaccharomyces pombe.
Methylglyoxal, a toxic metabolite synthesized in vivo during glycolysis, inhibits cell growth. One of the mechanisms protecting eukaryotic cells against its toxicity is the glyoxalase system, composed of glyoxalase I and II (glo1 and glo2), which converts methylglyoxal into d-lactic acid in the presence of glutathione. Here we have shown that the two principal oxidative stress response pathways of Schizosaccharomyces pombe, Sty1 and Pap1, are involved in the response to methylglyoxal toxicity. The mitogen-activated protein kinase Sty1 is phosphorylated and accumulates in the nucleus following methylglyoxal treatment. Moreover, glo2 expression is induced by methylglyoxal and environmental stresses in a Sty1-dependent manner. The transcription factor Pap1 also accumulates in the nucleus, activating the expression of its target genes following methylglyoxal treatment. Our studies showed that the C-terminal cysteine-rich domain of Pap1 is sufficient for methylglyoxal sensing. Furthermore, the redox status of Pap1 is not changed by methylglyoxal. We propose that methylglyoxal treatment triggers Pap1 and Sty1 nuclear accumulation, and we describe the molecular basis of such activation mechanisms. In addition, we discuss the potential physiological significance of these responses to a natural toxic metabolite.
Zuin
Alice
A
Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/Dr. Aiguader 80, 08003 Barcelona, Spain.
Vivancos
Ana P
AP
Sansó
Miriam
M
Takatsume
Yoshifumi
Y
Ayté
José
J
Inoue
Yoshiharu
Y
Hidalgo
Elena
E
D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D004352:Drug Resistance, Microbial; D015966:Gene Expression Regulation, Fungal; D006019:Glycolysis; D047468:Immunoprecipitation; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D000073718:Pancreatitis-Associated Proteins; D010641:Phenotype; D010766:Phosphorylation; D011765:Pyruvaldehyde / Q000494:pharmacology*; D012568:Schizosaccharomyces / Q000254:growth & development / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D014170:Transformation, Genetic
D050976:Basic-Leucine Zipper Transcription Factors; D000073718:Pancreatitis-Associated Proteins; C105096:Pap1 protein, S pombe; C000612141:REG3A protein, human; D029702:Schizosaccharomyces pombe Proteins; D011765:Pyruvaldehyde; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe