AFT1: a mediator of iron regulated transcriptional control in Saccharomyces cerevisiae.
Open accessAbstract
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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A comprehensive set of sequence analysis programs for the VAX
Devereux, J., Haeberli, P. E., & Smithies, O. (1984) · Nucleic Acids Research · doi:10.1093/nar/12.1part1.387 · Cited by 14,222 · see citing works
Transcriptional Regulation in Mammalian Cells by Sequence-Specific DNA Binding Proteins
Mitchell, P. J., & Tjian, R. (1989) · Science · doi:10.1126/science.2667136 · Cited by 3,046 · see citing works
Regulating the fate of mRNA: the control of cellular iron metabolism
Klausner, R. D., Rouault, T. A., & Harford, J. B. (1993) · Cell · doi:10.1016/0092-8674(93)90046-s · Cited by 1,210 · see citing works
Self-citationA Saccharomyces cerevisiae genomic plasmid bank based on a centromere-containing shuttle vector
Rose, M. D., Novick, P., Thomas, J. H., Botstein, D., & Fink, G. R. (1987) · Gene · doi:10.1016/0378-1119(87)90232-0 · Cited by 1,126 · see citing works
Yeast promoters and lacZ fusions designed to study expression of cloned genes in yeast.
Guarente, L. P. (1983) · Methods in Enzymology · doi:10.1016/0076-6879(83)01013-7 · Cited by 1,022 · see citing works
Tsai, S., Martin, D. I. K., Zon, L. I., D’Andrea, A. D., Wong, G. G., & Orkin, S. H. (1989) · Nature · doi:10.1038/339446a0 · Cited by 884 · see citing works
Obligatory Reduction of Ferric Chelates in Iron Uptake by Soybeans
Chaney, R. L., Brown, J. C., & Tiffin, L. O. (1972) · PLANT PHYSIOLOGY · doi:10.1104/pp.50.2.208 · Cited by 690 · see citing works
The FET3 gene of S. cerevisiae encodes a multicopper oxidase required for ferrous iron uptake.
Askwith, C., Eide, D., Van Ho, A., Bernard, P. S., Li, L., Davis-Kaplan, S., Sipe, D. M., & Kaplan, J. (1994) · Cell · doi:10.1016/0092-8674(94)90346-8 · Cited by 670 · see citing works
Dancis, A., Yuan, D. S., Haile, D., Askwith, C., Eide, D., Moehle, C., Kaplan, J., & Klausner, R. D. (1994) · Cell · doi:10.1016/0092-8674(94)90345-x · Cited by 659 · see citing works
Self-citationThe biochemical basis of the NADPH oxidase of phagocytes
Segal, A. W., & Abo, A. (1993) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(93)90051-n · Cited by 623 · see citing works
Bagg, A., & Neilands, J. B. (1987) · Biochemistry · doi:10.1021/bi00391a039 · Cited by 593 · see citing works
[27] Preparation of high molecular weight RNA
Köhrer, K., & Domdey, H. (1991) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(91)94030-g · Cited by 574 · see citing works
Molecular mechanism of regulation of siderophore-mediated iron assimilation
Bagg, A., & Neilands, J. B. (1987) · Microbiological Reviews · doi:10.1128/mr.51.4.509-518.1987 · Cited by 468 · see citing works
Isolation of the gene encoding the S. cerevisiae heat shock transcription factor
Wiederrecht, G., Seto, D., & Parker, C. S. (1988) · Cell · doi:10.1016/s0092-8674(88)91197-x · Cited by 427 · see citing works
Dancis, A., Haile, D. J., Yuan, D., & Klausner, R. D. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47300-0 · Cited by 400 · see citing works
Self-citationDancis, A., Roman, D. G., Anderson, G. J., Hinnebusch, A. G., & Klausner, R. D. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.9.3869 · Cited by 358 · see citing works
Self-citationKennedy, M. C., Mende‐Mueller, L., Blondin, G. A., & Beinert, H. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.24.11730 · Cited by 341 · see citing works
Haile, D. J., Rouault, T. A., Harford, J. B., Kennedy, M. C., Blondin, G. A., Beinert, H., & Klausner, R. D. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.24.11735 · Cited by 321 · see citing works
Self-citationGenetic Evidence that Ferric Reductase Is Required for Iron Uptake in Saccharomyces cerevisiae
Dancis, A., Klausner, R. D., Hinnebusch, A. G., & Barriocanal, J. G. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.5.2294-2301.1990 · Cited by 304 · see citing works
Self-citationLiu, H., Krizek, J., & Bretscher, A. P. (1992) · Genetics · doi:10.1093/genetics/132.3.665 · Cited by 284 · see citing works
Jungmann, J., Reins, H., Lee, J., Romeo, A. M., Hassett, R. F., Kosman, D. J., & Jentsch, S. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb06198.x · Cited by 283 · see citing works
Modular structure of transcription factors: Implications for gene regulation
Frankel, A. D., & Kim, P. S. (1991) · Cell · doi:10.1016/0092-8674(91)90378-c · Cited by 252 · see citing works
Georgatsou, E., & Alexandraki, D. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.5.3065-3073.1994 · Cited by 233 · see citing works
Engineered Metal-Binding Proteins: Purification to Protein Folding
Arnold, F. H., & Haymore, B. L. (1991) · Science · doi:10.1126/science.1648261 · Cited by 229 · see citing works
Eide, D. J., Davis-Kaplan, S. R., Jordan, I., Sipe, D. M., & Kaplan, J. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)36753-5 · Cited by 172 · see citing works
Nucleotide sequence of the iron regulatory gene fur
Schäffer, S., Hantke, K., & Braun, V. (1985) · Molecular and General Genetics MGG · doi:10.1007/bf00383321 · Cited by 163 · see citing works
Mei, B., Budde, A. D., & Leong, S. A. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.3.903 · Cited by 160 · see citing works
Iron Uptake by the Yeast Saccharomyces cerevisiae: Involvement of a Reduction Step
Lesuisse, E., Raguzzi, F., & Crichton, R. R. (1987) · Microbiology · doi:10.1099/00221287-133-11-3229 · Cited by 157 · see citing works
Philpott, C. C., Klausner, R. D., & Rouault, T. A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.15.7321 · Cited by 146 · see citing works
Self-citationRoman, D. G., Dancis, A., Anderson, G. J., & Klausner, R. D. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.7.4342 · Cited by 128 · see citing works
Self-citationInvestigation of a role for reduction in ferric iron uptake by mouse duodenum
Raja, K. B., Simpson, R. J., & Peters, T. J. (1992) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(92)90129-y · Cited by 124 · see citing works
Voisard, C., Wang, J., Mcevoy, J. L., Xu, P., & Leong, S. A. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.11.7091 · Cited by 116 · see citing works
Zhou, P. B., & Thiele, D. J. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.14.6112 · Cited by 102 · see citing works
Yeast RNA polymerase II subunit RPB9 is essential for growth at temperature extremes.
Woychik, N. A., Lane, W. S., & Young, R. A. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)55171-1 · Cited by 97 · see citing works
Voisard, C., Wang, J., Mcevoy, J. L., Xu, P., & Leong, S. A. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.11.7091-7100.1993 · Cited by 39 · see citing works
Bell, P. F., Chen, Y., Potts, W. E., et al. (1991) · Biological Trace Element Research · doi:10.1007/bf02990349 · Cited by 19 · see citing works
RCS1, a gene involved in controlling cell size in Saccharomyces cerevisiae
Gil, R., Zueco, J., Sentandreu, R., et al. (1991) · Yeast · doi:10.1002/yea.320070102 · Cited by 15 · see citing works
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Siderophore-Based Iron Acquisition and Pathogen Control
Miethke, M., & Marahiel, M. A. (2007) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00012-07 · Cited by 1,774 · see citing works
Regulation of Mitochondrial Iron Accumulation by Yfh1p, a Putative Homolog of Frataxin
Babcock, M., de Silva, D., Oaks, R., Davis-Kaplan, S., Jiralerspong, S., Montermini, L., Pandolfo, M., & Kaplan, J. (1997) · Science · doi:10.1126/science.276.5319.1709 · Cited by 921 · see citing works
A permease-oxidase complex involved in high-affinity iron uptake in yeast.
Stearman, R., Yuan, D. S., Yamaguchi-Iwai, Y., Klausner, R. D., & Dancis, A. (1996) · Science · doi:10.1126/science.271.5255.1552 · Cited by 683 · see citing works
Self-citationGrx5 Is a Mitochondrial Glutaredoxin Required for the Activity of Iron/Sulfur Enzymes
Rodrı́guez-Manzaneque, M. T., Tamarit, J., Bellı́, G., Ros, J., & Herrero, E. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.01-10-0517 · Cited by 464 · see citing works
CCC1 Is a Transporter That Mediates Vacuolar Iron Storage in Yeast
Li, L., Chen, O. S., Ward, D. M., & Kaplan, J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103944200 · Cited by 354 · see citing works
Haas, H. (2003) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-003-1335-2 · Cited by 334 · see citing works
Molecular mechanisms of iron uptake in fungi
Kosman, D. J. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03368.x · Cited by 331 · see citing works
Chen, C., Pande, K., French, S. D., Tuch, B. B., & Noble, S. M. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.07.005 · Cited by 314 · see citing works
Kemmeren, P., Sameith, K., van de Pasch, L. A. L., Benschop, J. J., Lenstra, T. L., Margaritis, T., O’Duibhir, E., Apweiler, E., van Wageningen, S., Ko, C. W., et al. (2014) · Cell · doi:10.1016/j.cell.2014.02.054 · Cited by 277 · see citing works
Response to Iron Deprivation in <i>Saccharomyces cerevisiae</i>
Philpott, C. C., & Protchenko, O. (2008) · Eukaryotic Cell · doi:10.1128/ec.00354-07 · Cited by 246 · see citing works
Iron use for haeme synthesis is under control of the yeast frataxin homologue (Yfh1)
Lesuisse, E. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg096 · Cited by 226 · see citing works
Chen, O. S., Crisp, R. J., Valachovic, M., Bard, M., Winge, D. R., & Kaplan, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403209200 · Cited by 202 · see citing works
Transcriptional Remodeling in Response to Iron Deprivation in<i>Saccharomyces cerevisiae</i>
Shakoury-Elizeh, M., Tiedeman, J., Rashford, J., Ferea, T., Demeter, J., Garcia, E., Rolfes, R., Brown, P. O., Botstein, D., & Philpott, C. C. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-09-0642 · Cited by 204 · see citing works
Knight, S. A. B., Sepuri, N. B. V., Pain, D., & Dancis, A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.29.18389 · Cited by 173 · see citing works
Self-citationFoury, F., & Roganti, T. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111789200 · Cited by 171 · see citing works
Hsu, P.-C., Yang, C.-Y., & Lan, C.-Y. (2011) · Eukaryotic Cell · doi:10.1128/ec.00158-10 · Cited by 157 · see citing works
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Yang, M., Cobine, P. A., Molik, S., Naranuntarat, A., Lill, R., Winge, D. R., & Culotta, V. C. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601064 · Cited by 143 · see citing works
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Synnott, J. M., Guida, A., Mulhern-Haughey, S., Higgins, D. G., & Butler, G. (2010) · Eukaryotic Cell · doi:10.1128/ec.00159-10 · Cited by 132 · see citing works
Cellular and mitochondrial remodeling upon defects in iron-sulfur protein biogenesis
Hausmann, A., Samans, B., Lill, R., & Mühlenhoff, U. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m705570200 · Cited by 111 · see citing works
Thomas, E., Roman, E., Claypool, S., Manzoor, N., Pla, J., & Panwar, S. L. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00889-13 · Cited by 105 · see citing works
Hu, C.-J., Bai, C., Zheng, X.-D., Wang, Y.-M., & Wang, Y. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204545200 · Cited by 97 · see citing works
Chen, C., & Noble, S. M. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002956 · Cited by 83 · see citing works
Ueta, R., Fujiwara, N., Iwai, K., & Yamaguchi-Iwai, Y. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00726-12 · Cited by 78 · see citing works
Self-citationHammacott, J. E., Williams, P. H., & Cashmore, A. M. (2000) · Microbiology · doi:10.1099/00221287-146-4-869 · Cited by 69 · see citing works
Ardon, O., Bussey, H., Philpott, C., Ward, D. M., Davis-Kaplan, S., Verroneau, S., Jiang, B., & Kaplan, J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m108701200 · Cited by 68 · see citing works
Lesuisse, E., Knight, S. A. B., Camadro, J., & Dancis, A. (2002) · Yeast · doi:10.1002/yea.840 · Cited by 56 · see citing works
Self-citationSantos, R., Buisson, N., Knight, S. A. B., Dancis, A., Camadro, J., & Lesuisse, E. (2004) · Molecular Microbiology · doi:10.1111/j.1365-2958.2004.04281.x · Cited by 55 · see citing works
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“Aft1 is a transcriptional regulator which induces transcription of genes involved in the recovery of iron upon iron starvation (22, 23).”
- Authors
- Yamaguchi‐Iwai, Y., Dancis, A., & Klausner, R. D.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Dancis, A.
- Venue
- The EMBO Journal
- Published
- 1995-03-01
- Volume
- 14
- Issue
- 6
- Pages
- 1231-1239
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC398200
- 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
- green
- europepmc.org
- 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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