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Upc2p and Ecm22p, Dual Regulators of Sterol Biosynthesis in Saccharomyces cerevisiae
Open accessAbstract
Sterol levels affect the expression of many genes in yeast and humans. We found that the paralogous transcription factors Upc2p and Ecm22p of yeast were sterol regulatory element (SRE) binding proteins (SREBPs) responsible for regulating transcription of the sterol biosynthetic genes ERG2 and ERG3. We defined a 7-bp SRE common to these and other genes, including many genes involved in sterol biosynthesis. Upc2p and Ecm22p activated ERG2 expression by binding directly to this element in the ERG2 promoter. Upc2p and Ecm22p may thereby coordinately regulate genes involved in sterol homeostasis in yeast. Ecm22p and Upc2p are members of the fungus-specific Zn[2]-Cys[6] binuclear cluster family of transcription factors and share no homology to the analogous proteins, SREBPs, that are responsible for transcriptional regulation by sterols in humans. These results suggest that Saccharomyces cerevisiae and human cells regulate sterol synthesis by different mechanisms.
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“Detailed analyses demonstrated the crucial role of these Upc2A-like factors in regulation of ERG gene biosynthesis [30,37,38] but little was known about the full range of their target genes.”
From The Candida glabrata Upc2A transcription factor is a global regulator of antifungal drug resistance pathways (2021) · cites this paper as [30]
In the citing paper
“At the same time, the levels of Upc2, and their association to ERG promoters, strongly increase, which finally results in the transcriptional induction of ERG genes [68,74].”
From Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae (2020) · cites this paper as [68]
In the citing paper
“Upon ergosterol depletion, the dissociation of the sterol ligand causes a conformational change that exposes Upc2 NLS, causing its translocation to the nucleus, where it activates the transcription of SRE/AR1c-containing genes including most ERG genes, sterol uptake genes (AUS1, PDR11), the DAN/TIR genes, which encode nine cell wall mannoproteins, and members of the seripauperin (PAU) gene family”
From Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae (2020) · cites this paper as [68]
In the citing paper
“During Saccharomycotina evolution, a member of the fungus specific Zn2-Cys6 binuclear cluster family of transcription factors called Upc2 displaced SREBP proteins as the major sterol regulator [68,69,70].”
From Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae (2020) · cites this paper as [68]
In the citing paper
“Under normal laboratory growth conditions, Ecm22 and, to a lesser extent, Upc2 bind to ERG gene promoters to maintain a basal expression level (Figure 3A) [68].”
From Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae (2020) · cites this paper as [68]
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Cites
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A Fungal Family of Transcriptional Regulators: the Zinc Cluster Proteins
MacPherson, S., Larochelle, M., & Turcotte, B. (2006) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00015-06 · Cited by 612
Exploration of Essential Gene Functions via Titratable Promoter Alleles
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Regulation of Sterol Synthesis in Eukaryotes
Espenshade, P. J., & Hughes, A. L. (2007) · Annual Review of Genetics · doi:10.1146/annurev.genet.41.110306.130315 · Cited by 593
Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae
Jordá, T., & Puig, S. (2020) · Genes · doi:10.3390/genes11070795 · Cited by 489
Badis, G., Chan, E. T., van Bakel, H., Peña‐Castillo, L., Tillo, D., Tsui, K., Carlson, C. D., Gossett, A. J., Hasinoff, M. J., Warren, C. L., et al. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.11.020 · Cited by 472
Metadata
- Authors
- Vik, Å., & Rine, J.
- Affiliations
- University of California, Berkeley (US)
- Corresponding author
- Rine, Jasper
- ORCID
- Rine, Jasper
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2001-10
- Volume
- 21
- Issue
- 19
- Pages
- 6395-6405
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC99787
- OpenAlex
- W2160849328
- Cited by
- 277
- References
- 33
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 18 · 2023: 9 · 2022: 17 · 2021: 11 · 2020: 14 · 2019: 10 · 2018: 9 · 2017: 12 · 2016: 7 · 2015: 8 · 2014: 12 · 2013: 15 · 2012: 8
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Norges Forskningsråd
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM035827, GM 35827)
- National Institute of Environmental Health Sciences (ESO1896, P30ES001896)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- sterol biosynthesis, sterol regulatory element, SREBP, transcriptional regulation, ERG2, ERG3, sterol homeostasis, Saccharomyces cerevisiae
- MeSH terms
- Cell Division, DNA-Binding Proteins, Fungal Proteins, Genes, Fungal, Oxidoreductases, Promoter Regions, Genetic, RNA, Fungal, Saccharomyces cerevisiae, Steroid Isomerases, Sterols, Transformation, Genetic, Transcriptional Activation, Trans-Activators, Gene Expression Regulation, Fungal, Response Elements, Saccharomyces cerevisiae Proteins
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