Probing the mechanism of FET3 repression by Izh2p overexpression

• Published in: Biochimica et biophysica acta 2007-07, Vol.1773 (7), p.1124-1132
• Main Authors: Kupchak, Brian R., Garitaonandia, Ibon, Villa, Nancy Y., Mullen, Matthew B., Weaver, Marilee G., Regalla, Lisa M., Kendall, Elizabeth A., Lyons, Thomas J.
• Format: Article
• Language: English
• Subjects: Adiponectin; AMP-Activated Protein Kinases; Ceruloplasmin - genetics; Ceruloplasmin - metabolism; Cyclic AMP - metabolism; Cyclic AMP-Dependent Protein Kinases - genetics; Cyclic AMP-Dependent Protein Kinases - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Epistasis, Genetic; FET3; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Fungal; Homeostasis; Iron - metabolism; IZH2; Membrane Proteins - genetics; Membrane Proteins - metabolism; Multienzyme Complexes - genetics; Multienzyme Complexes - metabolism; Osmotin; PAQR; Promoter Regions, Genetic; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; ras Proteins - genetics; ras Proteins - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2007.04.003

We previously reported a role for the IZH2 gene product in metal ion metabolism. Subsequently, Izh2p was also identified as a member of the PAQR family of receptors and, more specifically, as the receptor for the plant protein osmotin. In this report, we investigate the effect of Izh2p on iron homeostasis. We show that overproduction of Izh2p prevents the iron-dependent induction of the Fet3p component of the high-affinity iron-uptake system and is deleterious for growth in iron-limited medium. We demonstrate that the effect of Izh2p requires cAMP-dependent kinase and AMP-dependent kinase and is not mediated by general inhibition of the Aft1p iron-responsive transcriptional activator. We also show that Izh2p-overproduction negatively regulates Nrg1p/Nrg2p- and Msn2p/Msn4p-dependent reporters. Furthermore, we show that the Nrg1p/Nrg2p and Msn2p/Msn4p pairs are epistatic to each other with respect to their effects on FET3 expression. Finally, we show that the mechanism by which PAQR receptors activate signal transduction pathways is likely to be conserved from yeast to humans.