Tcn1p/Crz1p, a calcineurin-dependent transcription factor that differentially regulates gene expression in Saccharomyces cerevisiae
Open accessAbstract
Ca 2+ signals regulate gene expression in animal and yeast cells through mechanisms involving calcineurin, a protein phosphatase activated by binding Ca 2+ and calmodulin. Tcn1p, also named Crz1p, was identified as a transcription factor in yeast required for the calcineurin-dependent induction of PMC1, PMR1, PMR2A, and FKS2 which confer tolerance to high Ca 2+ , Mn 2+ , Na + , and cell wall damage, respectively. Tcn1p was not required for other calcineurin-dependent processes, such as inhibition of a vacuolar H + /Ca 2+ exchanger and inhibition of a pheromone-stimulated Ca 2+ uptake system, suggesting that Tcn1p functions downstream of calcineurin on a branch of the calcium signaling pathway leading to gene expression. Tcn1p contains three zinc finger motifs at its carboxyl terminus resembling the DNA-binding domains of Zif268, Swi5p, and other transcription factors. When fused to the transcription activation domain of Gal4p, the carboxy terminal domain of Tcn1p directed strong calcineurin-independent expression of PMC1–lacZ and other target genes. The amino-terminal domain of Tcn1p was found to function as a calcineurin-dependent transcription activation domain when fused to the DNA-binding domain of Gal4p. This amino-terminal domain also formed Ca 2+ -dependent and FK506-sensitive interactions with calcineurin in the yeast two-hybrid assay. These findings suggest that Tcn1p functions as a calcineurin-dependent transcription factor. Interestingly, induction of Tcn1p-dependent genes was found to be differentially controlled in response to physiological Ca 2+ signals generated by treatment with mating pheromone and high salt. We propose that different promoters are sensitive to variations in the strength of Ca 2+ signals generated by these stimuli and to effects of other signaling pathways.
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Calcineurin-dependent expression of ion transporting ATPases and a glucan synthase is regulated by the ScCrz1/Tcn1/Hal8 transcription factor.
“Calcineurin-dependent expression of these genes is regulated by the ScCrz1/Tcn1/Hal8 transcription factor (Stathopoulos and Cyert 1997;Matheos et al. 1997;Mendizabal et al. 1998)”
From Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor (2005) · cites this paper as Matheos et al. 1997
In the model and fission yeasts, the high-calcium hypersensitivity phenotype has been associated with decreased expression of the calcineurin-regulated PMC1 gene encoding the vacuolar calcium pump.
“In the model and fission yeasts, this phenotype has been associated to a decreased expression of the calcineurin-regulated PMC1 gene encoding the vacuolar calcium pump (Matheos et al. 1997;Hirayama et al. 2003).”
From Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor (2005) · cites this paper as Matheos et al. 1997
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Self-citation
- Authors
- Matheos, D. P., Kingsbury, T. J., Ahsan, U. S., & Cunningham, K. W.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1997-12-15
- Volume
- 11
- Issue
- 24
- Pages
- 3445-3458
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC316804
- OpenAlex
- W2080565111
- Cited by
- 332
- References
- 80
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 4 · 2023: 6 · 2022: 9 · 2021: 8 · 2020: 3 · 2019: 8 · 2018: 5 · 2017: 10 · 2016: 11 · 2015: 11 · 2014: 10 · 2013: 7 · 2012: 9
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- March of Dimes Foundation
- Chicago Community Trust
- Searle Scholars Program
- National Institutes of Health
- National Institute of General Medical Sciences (GM53082, R01GM053082)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- calcineurin, calcium signaling, transcription factors, zinc finger, transactivation domain, PMR1, FKS2, high salt stress, mating pheromone, Saccharomyces cerevisiae
- MeSH terms
- Calcium-Transporting ATPases, Amino Acid Sequence, beta-Galactosidase, Binding Sites, Calcium, DNA-Binding Proteins, Fungal Proteins, Glucosyltransferases, Membrane Proteins, Molecular Sequence Data, Pheromones, Saccharomyces cerevisiae, Transcription Factors, Trans-Activators, Gene Expression Regulation, Fungal, Genes, Reporter, Calcineurin, Saccharomyces cerevisiae Proteins, Plasma Membrane Calcium-Transporting ATPases
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