PreprintCited by 332Fungal and yeast genetics researchSignaling Pathways in DiseaseBacterial Genetics and Biotechnology

Tcn1p/Crz1p, a calcineurin-dependent transcription factor that differentially regulates gene expression in Saccharomyces cerevisiae

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Matheos, Dina P., Kingsbury, Tami J., Ahsan, U. Salma, Cunningham, Kyle W.·1997·Genes & Development

Abstract

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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Authors
Matheos, D. P., Kingsbury, T. J., Ahsan, U. S., & Cunningham, K. W.
Affiliations
Johns Hopkins University (US)
Venue
Genes & Development
Published
1997-12-15
Volume
11
Issue
24
Pages
3445-3458
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
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
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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