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

• Published in: Molecular microbiology Vol. 49; no. 2; pp. 457 - 468
• Main Authors: El Alami, Mohamed, Messenguy, Francine, Scherens, Bart, Dubois, Evelyne
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.07.2003; Blackwell Publishing Ltd
• Subjects: Gene Expression Regulation, Fungal; Genes, Reporter; Inositol Phosphates - metabolism; Nitrogen - metabolism; Oligonucleotide Array Sequence Analysis; Phosphotransferases (Alcohol Group Acceptor) - metabolism; Phosphotransferases (Phosphate Group Acceptor); Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Transcriptional Activation; Two-Hybrid System Techniques
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1046/j.1365-2958.2003.03562.x

Summary 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 arg82Δ or kcs1Δ 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.