Cited by 358Iron Metabolism and DisordersFungal and yeast genetics researchPlant Micronutrient Interactions and Effects

AFT1: a mediator of iron regulated transcriptional control in Saccharomyces cerevisiae.

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Yamaguchi‐Iwai, Y., Dancis, A., Klausner, R.D.·1995·The EMBO Journal

Abstract

Using a scheme for selecting mutants of Saccharomyces cerevisiae with abnormalities of iron metabolism, we have identified a gene, AFT1, that mediates the control of iron uptake. AFT1 encodes a 78 kDa protein with a highly basic amino terminal domain and a glutamine-rich C-terminal domain, reminiscent of transcriptional activators. The protein also contains an amino terminal and a C-terminal region with 10% His residues. A dominant mutant allele of this gene, termed AFT1-1up, results in high levels of ferric reductase and ferrous iron uptake that are not repressed by exogenous iron. The increased iron uptake is associated with enhanced susceptibility to iron toxicity. These effects may be explained by the failure of iron to repress transcription of FRE1, FRE2 and FET3. FRE1 and FRE2 encode plasma membrane ferric reductases, obligatory for ferric iron assimilation, and FET3 encodes a copper-dependent membrane-associated oxidase required for ferrous iron uptake. Conversely, a strain with interruption of the AFT1 gene manifests low ferric reductase and ferrous iron uptake and is susceptible to iron deprivation, because of deficient expression of FRE1 and negligible expression of FRE2 and FET3. Thus, AFT1 functions to activate transcription of target genes in response to iron deprivation and thereby plays a central role in iron homeostasis.

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Crossref · 10.1002/j.1460-2075.1995.tb07106.x

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Authors
Yamaguchi‐Iwai, Y., Dancis, A., & Klausner, R. D.
Affiliations
National Institutes of Health (US)
Venue
The EMBO Journal
Published
1995-03-01
Volume
14
Issue
6
Pages
1231-1239
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W2046440396
Cited by
358
References
37
Citations by year
2025: 5 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 5 · 2020: 11 · 2019: 5 · 2018: 11 · 2017: 12 · 2016: 6 · 2015: 9 · 2014: 7 · 2013: 15 · 2012: 14
FWCI
6.78
Type
journal article
Language
en
Open access
Locations
  • The EMBO Journal (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Micronutrient Interactions and Effects
Keywords
Aft1, iron homeostasis, iron absorption, ferric reductase, iron toxicity, iron starvation, transcriptional activator, Saccharomyces cerevisiae, mutant selection
MeSH terms
Amino Acid Sequence, Base Sequence, Biological Transport, Ceruloplasmin, Cloning, Molecular, Ferrous Compounds, Fungal Proteins, Genes, Fungal, Homeostasis, Molecular Sequence Data, Mutation, NADH, NADPH Oxidoreductases, Oxidoreductases, RNA, Fungal, RNA, Messenger, Saccharomyces cerevisiae, Transcription Factors, Transcription, Genetic, Restriction Mapping, Transcriptional Activation, Gene Expression Regulation, Fungal, Sequence Analysis, DNA, Saccharomyces cerevisiae Proteins, FMN Reductase

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