ArticleThe Journal of biological chemistry2009
Both Php4 function and subcellular localization are regulated by iron via a multistep mechanism involving the glutaredoxin Grx4 and the exportin Crm1.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 72 citations in OpenAlex.
- Functional characterization of Hul6 reveals a role in iron-dependent metabolism in Schizosaccharomyces pombe.Archives of microbiology · 2026Article
- The Hemoprotein Hhy1 Promotes Heme-Dependent Catalase Activity of Ctt1.Molecular microbiology · 2026Article
- Monothiol glutaredoxins in microbial iron metabolism: From iron-sulfur cluster trafficking to iron-dependent regulation.Advances in microbial physiology · 2026Review
- Fission yeast cells deficient in siderophore biosynthesis require Str2 for ferrichrome-dependent growth.Frontiers in microbiology · 2025Article
- The cytosolic form of dual localized BolA family protein Bol3 is important for adaptation to iron starvation inOpen biology · 2024Article
- Article
- Proteomic profiling of the monothiol glutaredoxin Grx3 reveals its global role in the regulation of iron dependent processes.PLoS genetics · 2020Article
- A fungal ABC transporter FgAtm1 regulates iron homeostasis via the transcription factor cascade FgAreA-HapX.PLoS pathogens · 2019Article
- The monothiol glutaredoxin GrxD is essential for sensing iron starvation in Aspergillus fumigatus.PLoS genetics · 2019Article
- Yeast AP-1 like transcription factors (Yap) and stress response: a current overview.Microbial cell (Graz, Austria) · 2019Review
- The Hap Complex in Yeasts: Structure, Assembly Mode, and Gene Regulation.Frontiers in microbiology · 2019Review
- The Monothiol Glutaredoxin Grx4 Regulates Iron Homeostasis and Virulence in Cryptococcus neoformans.mBio · 2018Article
- Schizosaccharomyces pombe Grx4 regulates the transcriptional repressor Php4 via [2Fe-2S] cluster binding.Metallomics : integrated biometal science · 2017Article
- Cytosolic iron chaperones: Proteins delivering iron cofactors in the cytosol of mammalian cells.The Journal of biological chemistry · 2017Review
- Arabidopsis Glutaredoxin S17 Contributes to Vegetative Growth, Mineral Accumulation, and Redox Balance during Iron Deficiency.Frontiers in plant science · 2017Article
- A Glutaredoxin·BolA Complex Serves as an Iron-Sulfur Cluster Chaperone for the Cytosolic Cluster Assembly Machinery.The Journal of biological chemistry · 2016Article
- Php4 Is a Key Player for Iron Economy in Meiotic and Sporulating Cells.G3 (Bethesda, Md.) · 2016Article
- Cellular sensing and transport of metal ions: implications in micronutrient homeostasis.The Journal of nutritional biochemistry · 2015Review
- Iron acquisition and oxidative stress response in aspergillus fumigatus.BMC systems biology · 2015Article
- Arabidopsis glutaredoxin S17 and its partner, the nuclear factor Y subunit C11/negative cofactor 2α, contribute to maintenance of the shoot apical meristem under long-day photoperiod.Plant physiology · 2015Article
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2 authors at 1 institution in 1 country.
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Abstract
In Schizosaccharomyces pombe, the CCAAT-binding factor is a multisubunit complex that contains the proteins Php2, Php3, Php4, and Php5. Under low iron conditions, Php4 acts as a negative regulatory subunit of the CCAAT-binding factor and fosters repression of genes encoding iron-using proteins. Under conditions of iron excess, Php4 expression is turned off by the iron-dependent transcriptional repressor Fep1. In this study, we developed a biological system that allows us to unlink iron-dependent behavior of Php4 protein from its transcriptional regulation by Fep1. Microscopic analyses revealed that a functional GFP-Php4 protein accumulates in the nucleus under conditions of iron starvation. Conversely, in cells undergoing a transition from low to high iron, GFP-Php4 is exported from the nucleus to the cytoplasm. We mapped a leucine-rich nuclear export signal that is necessary for nuclear exclusion of Php4. This latter process was blocked by leptomycin B. By using coimmunoprecipitation analysis, we showed that Php4 and Crm1 physically interact with each other. Although we determined that nuclear retention of Php4 per se is not sufficient to cause a constitutive repression of iron-using genes, we found that deletion of the grx4(+)-encoded glutaredoxin-4 renders Php4 constitutively active and invariably localized in the nucleus. Further analysis by bimolecular fluorescence complementation assay and by two-hybrid assays showed that Php4 and Grx4 are physically associated in vivo. Taken together, our findings indicate that Grx4 and Crm1 are novel components involved in the mechanism by which Php4 is inactivated by iron in a Fep1-independent manner.
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