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Cited by 153Fungal and yeast genetics researchIron Metabolism and DisordersPlant Micronutrient Interactions and Effects

A second iron-regulatory system in yeast independent of Aft1p

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Rutherford, Julian C., Jaron, Shulamit, Ray, Esha, Brown, Patrick O., Winge, Dennis R.·2001·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.261381198PMC PMC64680
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Abstract

Iron homeostasis in the yeast Saccharomyces cerevisiae is regulated at the transcriptional level by Aft1p, which activates the expression of its target genes in response to low-iron conditions. The yeast genome contains a paralog of AFT1, which has been designated AFT2 . To establish whether AFT1 and AFT2 have overlapping functions, a mutant containing a double aft1 Δ aft2 Δ deletion was generated. Growth assays established that the single aft2 Δ strain exhibited no iron-dependent phenotype. However, the double-mutant aft1 Δ aft2 Δ strain was more sensitive to low-iron growth conditions than the single-mutant aft1 Δ strain. A mutant allele of AFT2 ( AFT2 - 1 up ), or overexpression of the wild-type AFT2 gene, led to partial complementation of the respiratory-deficient phenotype of the aft1 Δ strain. The AFT2 - 1 up allele also increased the uptake of 59 Fe in an aft1Δ strain. DNA microarrays were used to identify genes regulated by AFT2 . Some of the AFT2 -regulated genes are known to be regulated by Aft1p; however, AFT2 - 1 up -dependent activation was independent of Aft1p. The kinetics of induction of two genes activated by the AFT2 - 1 up allele are consistent with Aft2p acting as a direct transcriptional factor. Truncated forms of Aft1p and Aft2p bound to a DNA duplex containing the Aft1p binding site in vitro . The wild-type allele of AFT2 activated transcription in response to growth under low-iron conditions. Together, these data suggest that yeast has a second regulatory pathway for the iron regulon, with AFT1 and AFT2 playing partially redundant roles.

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  • S. cerevisiae employs an iron regulatory system completely different from those employed by other fungi, with Aft1 as the major activator of iron uptake and recycling under iron restriction and Aft2 contributing redundantly.

    “S. cerevisiae employs an iron regulatory system completely different from those employed by other fungi. Here, Aft1 is the major activator of iron uptake and recycling under iron restriction conditions (21, 22), together with its paralog Aft2, which contributes in a largely redundant manner (23).”

    From A novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts (2016) · cites this paper as [23]

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Research works printed but not linked: 2

  1. [2]Yamaguchi-Iwai Y, Stearman R, Dancis A, Klausner R D. EMBO J. 1996;15:3377–3384. [PMC free article] [PubMed] [Google Scholar]
  2. [17]Eide D, Davis-Kaplan S, Jordan I, Sipe D, Kaplan J. J Biol Chem. 1992;267:20774–20781. [PubMed] [Google Scholar]

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Authors
Rutherford, J. C., Jaron, S., Ray, E., Brown, P. O., & Winge, D. R.
Affiliations
Howard Hughes Medical Institute (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2001-12-04
Volume
98
Issue
25
Pages
14322-14327
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.261381198
PMC
PMC64680
OpenAlex
W2010160980
Cited by
153
References
24
Citations by year
2026: 1 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 2 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 5 · 2014: 4 · 2013: 6 · 2012: 7
FWCI
4.20
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Newcastle University ePrints (Newcastle Univesity)
Funders
  • Howard Hughes Medical Institute
  • University of Utah
  • Huntsman Cancer Foundation
  • National Institutes of Health (5r01hg000983-06, 61286, ES03817)
  • National Human Genome Research Institute (HG-00983)
  • National Cancer Institute (CA 61286, 5 P30-CA42014, R01CA061286, P30CA042014)
  • National Institute of Environmental Health Sciences (R01ES003817, ES03817, R37ES003817)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Micronutrient Interactions and Effects
Keywords
iron homeostasis, transcriptional regulation, iron regulon, Saccharomyces cerevisiae, transcriptional activation, gene expression regulation, iron absorption, transcription factor binding, functional redundancy
MeSH terms
Alleles, Amino Acid Sequence, Base Sequence, Binding Sites, DNA, Fungal, Fungal Proteins, Genes, Fungal, Homeostasis, Iron, Molecular Sequence Data, Phenotype, Promoter Regions, Genetic, Protein Binding, Saccharomyces cerevisiae, Transcription Factors, Trans-Activators, Gene Expression, Gene Deletion, Sequence Homology, Amino Acid, Oligonucleotide Array Sequence Analysis, Saccharomyces cerevisiae Proteins

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