Recognition of galactose by a scaffold protein recruits a transcriptional activator for the GAL regulon induction in Candida albicans
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Abstract
Abstract The GAL pathway of yeasts has long served as a model system for understanding of how regulatory mode of eukaryotic metabolic pathways evolves. While Gal4 mode has been well-characterized in Saccharomycetaceae clade, little is known about the regulation of the GAL pathway in other yeasts. Here, we find that Rep1, a Ndt80-like family transcription factor, serves as a galactose sensor in the commensal-pathogenic fungus Candida albicans . It is presented at the GAL gene promoters independent of the presence of galactose. Rep1 recognizes galactose via a direct physical interaction. The net result of this interaction is the recruitment of a transcriptional activator Cga1 (Candida galactose gene activator, orf19.4959) and transcription of the GAL genes proceeds. Rep1 and Cga1 are conserved across the CTG species. Rep1 itself does not possess transcriptional activity. Instead, it provides a scaffold to recruit different factors for transcriptional regulation. Rep1-Cga1 mode of regulation represents a new example of network rewiring in fungi, which provides insight into how C. albicans evolves transcriptional programs to colonize diverse host niches.
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A Rep1 scaffold coupled with the Cga1 transcription activator is the pivotal regulator of galactose signaling in Serinales, including C. albicans, and CaRtg1 and CaRtg3 are required for growth on galactose only upon inhibition of respiration.
“a later report demonstrated that a Rep1 scaffold coupled with the Cga1 transcription activator is the pivotal regulator of galactose signaling in Serinales, including C. albicans, and CaRtg1 and CaRtg3 are required for growth on galactose only upon inhibition of respiration”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Sun et al. 2023
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Experimental — accuracy not yet measuredRtg transcription factors partially replace Gal4p of S. cerevisiae as regulators of galactose catabolism genes in cells with inhibited respiration.
“In a classic example of evolutionary rewiring of transcriptional control, they partially replace Gal4p of S. cerevisiae as the regulators of galactose catabolism genes in cells with inhibited respiration (Dalal et al. 2016; Sun et al. 2023).”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Sun et al. 2023
The Results section ('Rep1 is required for galactose signaling in C. albicans'; page unavailable) reports that Rtg1 and Rtg3 were implicated in galactose catabolism and that their mutants had growth defects on galactose when respiration was inhibited with Antimycin A. It does not establish that they replace Gal4 as regulators of galactose catabolism genes; instead, it reports normal GAL1 and GAL10 induction in the mutants under the conditions tested and identifies Rep1 as the pivotal regulator. (LLM, conf=0.84)
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References 51 · Cited by 9
- Authors
- Sun, X., Yu, J., Zhu, C., Mo, X., Sun, Q., Yang, D., Su, C., & Lu, Y.
- Affiliations
- Wuhan University (CN)
- Tianjin University (CN)
- College of Life Sciences, TaiKang Center for Life and Medical Sciences, Wuhan University
- Corresponding author
- Su, Chang
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2023-02-01
- Volume
- 12
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC9925049
- OpenAlex
- W4318754306
- Cited by
- 9
- References
- 51
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 2
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (32070074, 32170089, 81973370)
- Natural Science Foundation of Hubei Province (2022CFB103)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Candida albicans, REP1, transcriptional regulation, transcriptional activator, protein-protein interaction, scaffold proteins, network rewiring, galactose metabolism
- MeSH terms
- Candida albicans, Galactose, Promoter Regions, Genetic, Transcription Factors, Gene Expression Regulation, Fungal, Regulon
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