Evidence map›Paper›PMID 18281282›Full record

ArticleThe Journal of biological chemistry2008

Identification of FRA1 and FRA2 as genes involved in regulating the yeast iron regulon in response to decreased mitochondrial iron-sulfur cluster synthesis.

Attila Kumánovics, Opal S Chen, Liangtao Li, Dustin Bagley, Erika M Adkins, Huilan Lin, Nin N Dingra, Caryn E Outten, Greg Keller, Dennis Winge and 2 more

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

117 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Requirements for the biogenesis of [2Fe-2S] proteins in the human and yeast cytosol.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  5. Review
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  14. Aminopeptidases trim Xaa-Pro proteins, initiating their degradation by the Pro/N-degron pathway.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article

57 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Attila KumánovicsDepartment of Pathology and Departments of Biochemistry and Medicine, School of Medicine, University of Utah, Salt Lake City Utah 84132, USA.
Opal S Chen
Liangtao Li
Dustin Bagley
Erika M Adkins
Huilan Lin
Nin N Dingra
Caryn E Outten
Greg Keller
Dennis Winge
Diane M Ward
Jerry Kaplan

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jared P Rutter · 1986 to 2026
$72.6M
RESEARCH TRAINING IN HEMATOLOGYT32DK007115 · NIDDK · UNIVERSITY OF UTAH · PI LEIBOLD, ELIZABETH ANN, PRCHAL, JOSEF T · 1986 to 2020
$8.4M
The Genetic Analysis of Mitochondrial Iron MetabolismR01DK052380 · NIDDK · UNIVERSITY OF UTAH · PI WARD, DIANE MCVEY · 1998 to 2016
$5.6M
FACTORS REGULATING THE CELLULAR UPTAKE OF IRONR37DK030534 · NIDDK · UNIVERSITY OF UTAH · PI KAPLAN, JERRY · 2000 to 2009
$3.3M
FACTORS REGULATING THE CELLULAR UPTAKE OF IRONR01DK030534 · NIDDK · UNIVERSITY OF UTAH · PI WARD, DIANE MCVEY · 1986 to 2018
$2.7M
Metal Homeostatic Mechanisms in YeastR01GM083292 · NIGMS · UNIVERSITY OF UTAH · PI WINGE, DENNIS R. · 2008 to 2011
$1.2M
Mitochondrial Anti-Oxidant Factors and Redox StatusK22ES013780 · NIEHS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI OUTTEN, CARYN E · 2005 to 2007
$315k
NCI NIH HHS P30CA 42014NIDDK NIH HHS DK30534NIDDK NIH HHS DK52380NIDDK NIH HHS T32 DK07115-29NIEHS NIH HHS ES13780NIEHS NIH HHS K22 ES013780NIGMS NIH HHS GM083292PHS HHS 5P30KD72437
6 · The paper itself

Abstract

The nature of the connection between mitochondrial Fe-S cluster synthesis and the iron-sensitive transcription factor Aft1 in regulating the expression of the iron transport system in Saccharomyces cerevisiae is not known. Using a genetic screen, we identified two novel cytosolic proteins, Fra1 and Fra2, that are part of a complex that interprets the signal derived from mitochondrial Fe-S synthesis. We found that mutations in FRA1 (YLL029W) and FRA2 (YGL220W) led to an increase in transcription of the iron regulon. In cells incubated in high iron medium, deletion of either FRA gene results in the translocation of the low iron-sensing transcription factor Aft1 into the nucleus, where it occupies the FET3 promoter. Deletion of either FRA gene has the same effect on transcription as deletion of both genes and is not additive with activation of the iron regulon due to loss of mitochondrial Fe-S cluster synthesis. These observations suggest that the FRA proteins are in the same signal transduction pathway as Fe-S cluster synthesis. We show that Fra1 and Fra2 interact in the cytosol in an iron-independent fashion. The Fra1-Fra2 complex binds to Grx3 and Grx4, two cytosolic monothiol glutaredoxins, in an iron-independent fashion. These results show that the Fra-Grx complex is an intermediate between the production of mitochondrial Fe-S clusters and transcription of the iron regulon.

Indexed as

MutationActive Transport, Cell NucleusCell NucleusCytosolFungal ProteinsGene DeletionGenetic Complementation TestIntracellular Signaling Peptides and ProteinsIronIron-Sulfur ProteinsMitochondriaModels, BiologicalModels, GeneticPlasmidsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsFRA1 protein, S cerevisiaeFRA2 protein, S cerevisiaeFungal ProteinsIntracellular Signaling Peptides and ProteinsIronIron-Sulfur ProteinsSaccharomyces cerevisiae Proteins

Identifiers

PMID18281282
PMCPMC2447656

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.