title: Arg82p is a bifunctional protein whose inositol polyphosphate kinase activity is essential for nitrogen and PHO gene expression but not for Mcm1p chaperoning in yeast.
abstract: In Saccharomyces cerevisiae, the synthesis of inositol pyrophosphates is essential for vacuole biogenesis and the cell's response to certain environmental stresses. The kinase activity of Arg82p and Kcs1p is required for the production of soluble inositol phosphates. To define physiologically relevant targets of the catalytic products of Arg82p and Kcs1p, we used DNA microarray technology. In arg82delta or kcs1delta cells, we observed a derepressed expression of genes regulated by phosphate (PHO) on high phosphate medium and a strong decrease in the expression of genes regulated by the quality of nitrogen source (NCR). Arg82p and Kcs1p are required for activation of NCR-regulated genes in response to nitrogen availability, mainly through Nil1p, and for repression of PHO genes by phosphate. Only the catalytic activity of both kinases was required for PHO gene repression by phosphate and for NCR gene activation in response to nitrogen availability, indicating a role for inositol pyrophosphates in these controls. Arg82p also controls expression of arginine-responsive genes by interacting with Arg80p and Mcm1p, and expression of Mcm1-dependent genes by interacting with Mcm1p. We show here that Mcm1p and Arg80p chaperoning by Arg82p does not involve the inositol polyphosphate kinase activity of Arg82p, but requires its polyaspartate domain. Our results indicate that Arg82p is a bifunctional protein whose inositol kinase activity plays a role in multiple signalling cascades, and whose acidic domain protects two MADS-box proteins against degradation.
authors.affiliation: Institut de Recherches Microbiologiques J-M Wiame, Laboratoire de Microbiologie de l'Université Libre de Bruxelles, 1 avenue Emile Gryzon, 1070 Bruxelles, Belgium.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Alami
authors.forename: Francine
authors.initials: F
authors.lastname: Messenguy
authors.forename: Bart
authors.initials: B
authors.lastname: Scherens
authors.forename: Evelyne
authors.initials: E
authors.lastname: Dubois
mesh_terms: D015966:Gene Expression Regulation, Fungal; D017930:Genes, Reporter; D007295:Inositol Phosphates / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D017856:Phosphotransferases (Phosphate Group Acceptor); D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
chemical_list: D007295:Inositol Phosphates; D029701:Saccharomyces cerevisiae Proteins; C425775:ARG82 protein, S cerevisiae; D017853:Phosphotransferases (Alcohol Group Acceptor); C434257:inositol polyphosphate multikinase; D017856:Phosphotransferases (Phosphate Group Acceptor); C098863:KCS1 protein, S cerevisiae; D009584:Nitrogen