At acidic pH, the GPA2-cAMP pathway is necessary to counteract the ORD1-mediated repression of the hypoxic SRP1/TIR1 yeast gene.
The hypoxic SRP1/TIR1 gene encodes a stress-response cell wall mannoprotein and this gene is downregulated at acidic pH. The stress-responsive HOG pathway is necessary to maintain hypoxic TIR1 expression, but only at acidic pH. However, unlike known HOG pathway-dependent genes, TIR1 is under positive cAMP control and this effect is mediated by GPA2 but not by RAS2. Genetic analysis showed that ord1 mutation was epistatic to the gpa2 mutation, thereby indicating that Gpa2p is needed to counteract the Ord1 factor, which is involved in the repression of hypoxic TIR1 expression, while the HOG pathway appears to be independent from Ord1 repression. In addition, an increased ORD1 gene expression was observed in the Deltagpa2 mutant cells, meaning that GPA2 maintains a low basal level of ORD1 transcripts. Thus, cAMP allows partial relief of the TIR1 repression exerted by Ord1p. However, this is contradicted at acidic pH by the HOG pathway requirement because Hog1p is activated under stress conditions when the cAMP cellular content is low. The opposite effects of the GPA2-cAMP and HOG pathways are likely to explain the diminished hypoxic expression of TIR1 at acidic pH.
Bourdineaud
J P
JP
Faculté d'Oenologie, Université de Bordeaux II, 351 cours de la Libération, 33405 Talence Cedex, France. jean-paul.bourdineaud@oenologie.u-bordeaux.fr
D000242:Cyclic AMP / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism*; D044385:GTP-Binding Protein alpha Subunits; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D020928:Mitogen-Activated Protein Kinases; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D010100:Oxygen / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D044385:GTP-Binding Protein alpha Subunits; D006360:Heat-Shock Proteins; D006609:High Mobility Group Proteins; C082364:IXR1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C491115:TIR1 protein, S cerevisiae; D000242:Cyclic AMP; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; C083907:Gpa2 protein, S cerevisiae; D020962:Heterotrimeric GTP-Binding Proteins; D010100:Oxygen