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A Mutation in a Purported Regulatory Gene Affects Control of Sterol Uptake in Saccharomyces cerevisiae
Open accessAbstract
Aerobically growing wild-type strains of Saccharomyces cerevisiae are unable to take exogenously supplied sterols from media. This aerobic sterol exclusion is vitiated under anaerobic conditions, in heme-deficient strains, and under some conditions of impaired sterol synthesis. Mutants which can take up sterols aerobically in heme-competent cells have been selected. One of these mutations, designated upc2-1, gives a pleiotropic phenotype in characteristics as diverse as aerobic accumulation of sterols, total lipid storage, sensitivity to metabolic inhibitors, response to altered sterol structures, and cation requirements. During experiments designed to ascertain the effects of various cations on yeast with sterol alterations, it was observed that upc2-1 was hypersensitive to Ca2+. Using resistance to Ca2+ as a screening vehicle, we cloned UPC2 and showed that it is YDR213W, an open reading frame on chromosome IV. This belongs to a fungal regulatory family containing the Zn(II)2Cys6 binuclear cluster DNA binding domain. The single guanine-to-adenine transition in upc2-1 gives a predicted amino acid change from glycine to aspartic acid. The regulatory defect explains the semidominance and pleiotropic effects of upc2-1.
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“ERG11 is transcriptionally regulated by the zinc cluster transcription factor Upc2.”
From Gain-of-Function Mutations in UPC2 Are a Frequent Cause of ERG11 Upregulation in Azole-Resistant Clinical Isolates of Candida albicans (2012) · cites this paper as [4]
Experimental — accuracy not yet measuredIn the citing paper
“The relevant mutation (upc2-1) [19] is a change of a glycine to an aspartate residue located at position (G888D) in the carboxy-terminus of ScUpc2.”
From The Candida glabrata Upc2A transcription factor is a global regulator of antifungal drug resistance pathways (2021) · cites this paper as [19]
In the citing paper
“The S. cerevisiae UPC2-1 allele, from which we derived the G898D UPC2A, was originally isolated on the basis of permitting aerobic sterol uptake [19].”
From The Candida glabrata Upc2A transcription factor is a global regulator of antifungal drug resistance pathways (2021) · cites this paper as [19]
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Arens, J., Bergs, D., Mewes, M., Merz, J., Schembecker, G., & Schulz, F. (2014) · Mycology: An International Journal on Fungal Biology · doi:10.1080/21501203.2014.917735 · Cited by 7
Leak, F. W., Tove, S. R., & Parks, L. W. (1999) · DNA and Cell Biology · doi:10.1089/104454999315510 · Cited by 7
Self-citationSanglard, D. (2011) · Current Fungal Infection Reports · doi:10.1007/s12281-011-0055-9 · Cited by 6
Moretti-Almeida, G., Netto, L. E. S., & Monteiro, G. (2013) · FEBS Letters · doi:10.1016/j.febslet.2013.07.024 · Cited by 6
Metadata
- Authors
- Crowley, J. H., Leak, F. W., Shianna, K. V., Tove, S., & Parks, L. W.
- Affiliations
- North Carolina State University (US)
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 1998-08-15
- Volume
- 180
- Issue
- 16
- Pages
- 4177-4183
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- PMC
- PMC107415
- OpenAlex
- W2159654630
- Cited by
- 123
- References
- 26
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 3 · 2018: 4 · 2017: 5 · 2015: 3 · 2014: 4 · 2013: 10 · 2012: 2
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Bacteriology (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs (TPP 97-003)
- Agricultural Research Service
- Army Research Office
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- sterol uptake, UPC2, Saccharomyces cerevisiae, heme deficiency, sterol biosynthesis, pleiotropic mutations, calcium sensitivity, fat deposition, semi-dominant mutation
- MeSH terms
- Amino Acid Sequence, Base Sequence, Calcium, Fungal Proteins, Genes, Fungal, Genes, Regulator, Genetic Complementation Test, Molecular Sequence Data, Mutation, Saccharomyces cerevisiae, Sterols, Trans-Activators, Open Reading Frames, Saccharomyces cerevisiae Proteins
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