Transcription factors CgUPC2A and CgUPC2B regulate ergosterol biosynthetic genes in Candida glabrata: Gene expression in sterol-depleted Candida
Open accessAbstract
Zn[2]-Cys[6] binuclear transcription factors Upc2p and Ecm22p regulate the expression of genes involved in ergosterol biosynthesis and exogenous sterol uptake in Saccharomyces cerevisiae. We identified two UPC2/ECM22 homologues in the pathogenic fungus Candida glabrata which we designated CgUPC2A and CgUPC2B. The contribution of these two genes to sterol homeostasis was investigated. Cells that lack CgUPC2A (upc2AΔ) exhibited enhanced susceptibility to the sterol biosynthesis inhibitors, fluconazole and lovastatin, whereas upc2BΔ-mutant cells were as susceptible to the drugs as wild-type cells. The growth of upc2AΔ cells was also severely attenuated under anaerobic conditions. Lovastatin treatment enhanced the expression of ergosterol biosynthetic genes, ERG2 and ERG3 in wild-type and upc2BΔ but not in upc2AΔ cells. Similarly, serum-induced expression of ERG2 and ERG3 was completely impaired in upc2AΔ cells but was unaffected in upc2BΔ cells, whereas serum-induced expression of the sterol transporter gene CgAUS1 was impaired in both upc2AΔ and upc2BΔ cells. These results suggest that in C. glabrata CgUPC2A but not in CgUPC2B is the main transcriptional regulator of the genes responsible for maintaining sterol homeostasis as well as susceptibility to sterol inhibitors.
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The interaction between Upc2A and the FKS1 gene provides a connection between azole resistance and echinocandin resistance.
“The finding of the interaction between Upc2A and the FKS1 gene provides an interesting connection between azole resistance, well-known to be impacted by Upc2A [40], and echinocandin resistance.”
From The Candida glabrata Upc2A transcription factor is a global regulator of antifungal drug resistance pathways (2021) · cites this paper as [40]
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- Authors
- Nagi, M., Nakayama, H., Tanabe, K., Bard, M., Aoyama, T., Okano, M., Higashi, S., Ueno, K., Chibana, H., Niimi, M., Yamagoe, S., Umeyama, T., Kajiwara, S., Ohno, H., & Miyazaki, Y.
- Affiliations
- Tokyo Institute of Technology (JP)
- Suzuka University of Medical Science (JP)
- National Institute of Infectious Diseases (JP)
- Indiana University – Purdue University Indianapolis (US)
- National Institute of Technology, Suzuka College (JP)
- Chiba University (JP)
- Corresponding author
- Tanabe, Koichi
- ORCID
- Venue
- Genes to Cells
- Publisher
- Wiley
- Published
- 2010-12-27
- Volume
- 16
- Issue
- 1
- Pages
- 80-89
- ISSN
- 1356-9597 (ISSN-L)
- OpenAlex
- W1726796702
- Cited by
- 68
- References
- 22
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 4 · 2022: 9 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 7 · 2017: 5 · 2016: 4 · 2015: 1 · 2014: 7 · 2013: 4 · 2012: 2
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes to Cells (publishedVersion)
- PubMed (publishedVersion)
- Tokyo Tech Research Repository (Tokyo Institute of Technology) (submittedVersion)
- Funders
- Japan Health Sciences Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- Candida glabrata, ergosterol biosynthesis, sterol homeostasis, sterol uptake, ERG2, ERG3, fluconazole susceptibility, serum-induced gene expression, anaerobic growth, fungal pathogenicity
- MeSH terms
- Antifungal Agents, Ergosterol, Fungal Proteins, Genes, Fungal, Lovastatin, Sterols, Transcription Factors, Trans-Activators, Fluconazole, Gene Expression Regulation, Fungal, Saccharomyces cerevisiae Proteins, Candida glabrata
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