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PMID: 17553578 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Probing the mechanism of FET3 repression by Izh2p overexpression.

Biochimica et biophysica acta ·Vol. 1773 ·No. 7 ·2007-07-00 ·Pages 1124-32

Kupchak BR, Garitaonandia I, Villa NY, Mullen MB, Weaver MG, Regalla LM, Kendall EA, Lyons TJ

Abstract

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.

MeSH Terms
AMP-Activated Protein Kinases Ceruloplasmin/genetics,metabolism Cyclic AMP/metabolism Cyclic AMP-Dependent Protein Kinases/genetics,metabolism DNA-Binding Proteins/genetics,metabolism Epistasis, Genetic Gene Expression Regulation, Enzymologic Gene Expression Regulation, Fungal Homeostasis Iron/metabolism Membrane Proteins/genetics,metabolism Multienzyme Complexes/genetics,metabolism Promoter Regions, Genetic Protein Serine-Threonine Kinases/genetics,metabolism Repressor Proteins/genetics,metabolism Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism Transcription Factors/genetics,metabolism ras Proteins/genetics,metabolism
Chemicals
AFT1 protein, S cerevisiae DNA-Binding Proteins IZH2 protein, S cerevisiae MSN2 protein, S cerevisiae MSN4 protein, S cerevisiae Membrane Proteins Multienzyme Complexes NRG1 protein, S cerevisiae Nrg2 protein, S cerevisiae Repressor Proteins Saccharomyces cerevisiae Proteins Transcription Factors Cyclic AMP Iron Ceruloplasmin FET3 protein, S cerevisiae Protein Serine-Threonine Kinases Cyclic AMP-Dependent Protein Kinases AMP-Activated Protein Kinases ras Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kupchak Brian R
Department of Chemistry, University of Florida, P.O. Box 117200, Gainesville, FL 32611, USA.
Garitaonandia Ibon
Villa Nancy Y
Mullen Matthew B
Weaver Marilee G
Regalla Lisa M
Kendall Elizabeth A
Lyons Thomas J
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Article Info
Journal
Biochimica et biophysica acta
Abbr.
Biochim Biophys Acta
ISSN
0006-3002
DOI
10.1016/j.bbamcr.2007.04.003
Published
2007-07-00
Epub
2007-00-13
Pages
1124-32
Language
English
Region
Netherlands
NLM ID
0217513
PMCID
PMC1994572
Subset
IM
Grants
NIDDK NIH HHS · R21 DK074812 · United States
NIDDK NIH HHS · R21 DK074812-01 · United States
NIDDK NIH HHS · R21 DK074812-02 · United States
NIDDK NIH HHS · 1R21DK074812-01 · United States
External Links
PubMed source DOI: 10.1016/j.bbamcr.2007.04.003 PMC Full Text
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