Probing the mechanism of FET3 repression by Izh2p overexpression.
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.
Kupchak
Brian R
BR
Department of Chemistry, University of Florida, P.O. Box 117200, Gainesville, FL 32611, USA.
Garitaonandia
Ibon
I
Villa
Nancy Y
NY
Mullen
Matthew B
MB
Weaver
Marilee G
MG
Regalla
Lisa M
LM
Kendall
Elizabeth A
EA
Lyons
Thomas J
TJ
D055372:AMP-Activated Protein Kinases; D002570:Ceruloplasmin / Q000235:genetics / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004843:Epistasis, Genetic; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D006706:Homeostasis; D007501:Iron / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
C090297:AFT1 protein, S cerevisiae; D004268:DNA-Binding Proteins; C497767:IZH2 protein, S cerevisiae; C081935:MSN2 protein, S cerevisiae; C081937:MSN4 protein, S cerevisiae; D008565:Membrane Proteins; D009097:Multienzyme Complexes; C117881:NRG1 protein, S cerevisiae; C435344:Nrg2 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000242:Cyclic AMP; D007501:Iron; D002570:Ceruloplasmin; C085513:FET3 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D055372:AMP-Activated Protein Kinases; D018631:ras Proteins