Cytoplasmic localization of sterol transcription factors Upc2p and Ecm22p in S. cerevisiae

Marie, Chelsea; Leyde, Sarah; White, Theodore C.

doi:10.1016/j.fgb.2008.07.004

Cited by 47Fungal and yeast genetics researchAntifungal resistance and susceptibilityCancer, Lipids, and Metabolism

Cytoplasmic localization of sterol transcription factors Upc2p and Ecm22p in S. cerevisiae

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Marie, Chelsea, Leyde, Sarah, White, Theodore C.·2008·Fungal Genetics and Biology

DOI 10.1016/j.fgb.2008.07.004PMC PMC2580778

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Abstract

Ergosterol homeostasis is a critical process for fungal cells. Paralogous zinc cluster transcription factors Upc2p and Ecm22p are major regulators of ergosterol biosynthesis in Saccharomyces cerevisiae. Upc2p and Ecm22p sense and respond to sterol depletion but their mechanism of activation has not been defined. Subcellular localization and functional expression of Upc2p-GFP and Ecm22p-GFP was monitored by fluorescence microscopy and flow cytometry in live yeast cells. Both fusion proteins localized to intracellular membranes and to perinuclear foci. Perinuclear localization of Upc2p-GFP and Ecm22p-GFP was increased when ergosterol biosynthesis was blocked by azole drug treatment. Nuclear localization in response to sterol depletion is consistent with the hypothesis that Upc2p and Ecm22p are trafficked from a membrane to the nucleus as a post-translational mechanism of sterol sensing.

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ScUpc2 and ScEcm22 are localized to intracellular membranes outside the nucleus, and under sterol-depleting conditions, perinuclear localization is increased.
“Previous work in S. cerevisiae shows that ScUpc2 and ScEcm22 are localized to intracellular membranes outside the nucleus, and under sterol-depleting conditions, perinuclear localization is increased (20).”
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 [20]
Under normal conditions, the binding of ergosterol to a deep hydrophobic pocket within Upc2 CTD retains the transcription factor in the cytosol in its repressed form.
“Under normal conditions, the binding of ergosterol to a deep hydrophobic pocket within Upc2 CTD retains the transcription factor in the cytosol in its repressed form, probably because sterol binding masks its bipartite amino-terminal nuclear localization signal (NLS) or because of its interaction with a hypothetical cytosolic protein (Figure 2B) [71,72].”
From Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae (2020) · cites this paper as [72]

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Davies, B. S. J., Wang, H. S., & Rine, J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.16.7375-7385.2005 · Cited by 138 · see citing works
Upc2p and Ecm22p, Dual Regulators of Sterol Biosynthesis in Saccharomyces cerevisiae
Vik, Å., & Rine, J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.19.6395-6405.2001 · Cited by 277 · see citing works
Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae
Jordá, T., & Puig, S. (2020) · Genes · doi:10.3390/genes11070795 · Cited by 489 · see citing works

Authors: Marie, C., Leyde, S., & White, T. C.
Affiliations: University of Washington (US)
Center for Infectious Disease Research (US)
Corresponding author: White, Theodore C.
ORCID: Marie, Chelsea
Leyde, Sarah
White, Theodore C.
Venue: Fungal Genetics and Biology
Publisher: Elsevier BV
Published: 2008-10
Volume: 45
Issue: 10
Pages: 1430-1438
ISSN: 1087-1845 (ISSN-L)
DOI: 10.1016/j.fgb.2008.07.004
PMC: PMC2580778
OpenAlex: W2159939027
Cited by: 47
References: 35
Citations by year: 2025: 3 · 2024: 6 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 3 · 2015: 4 · 2014: 1 · 2013: 4 · 2012: 2
FWCI: 2.19
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Fungal Genetics and Biology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute of Dental and Craniofacial Research (R01DE011367, R01DE017078, R01 DE17078, R01 DE-11367, R01 DE 14161, R01DE014161)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords: zinc cluster transcription factors, sterol homeostasis, ergosterol biosynthesis, subcellular localization, nuclear localization, sterol sensing, Saccharomyces cerevisiae
MeSH terms: Azoles, Cytoplasm, Ergosterol, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Transcription Factors, Trans-Activators, Protein Transport, Saccharomyces cerevisiae Proteins, Green Fluorescent Proteins

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Cytoplasmic localization of sterol transcription factors Upc2p and Ecm22p in S. cerevisiae

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