Calcineurin acts through the CRZ1/TCN1-encoded transcription factor to regulate gene expression in yeast

Stathopoulos, Angelike M.; Cyert, Martha S.

doi:10.1101/gad.11.24.3432

PreprintCited by 442Fungal and yeast genetics researchSignaling Pathways in DiseaseBacterial Genetics and Biotechnology

Calcineurin acts through the CRZ1/TCN1-encoded transcription factor to regulate gene expression in yeast

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Stathopoulos, Angelike M., Cyert, Martha S.·1997·Genes & Development

DOI 10.1101/gad.11.24.3432PMC PMC316814

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Abstract

Calcineurin is a conserved Ca2+/calmodulin-dependent protein phosphatase that plays a critical role in Ca2+ signaling. We describe new components of a calcineurin-mediated response in yeast, the Ca2+-induced transcriptional activation of FKS2, which encodes a beta-1,3 glucan synthase. A 24-bp region of the FKS2 promoter was defined as sufficient to confer calcineurin-dependent transcriptional induction on a minimal promoter in response to Ca2+ and was named CDRE (for calcineurin-dependent response element). The product of CRZ1 (YNL027w) was identified as an activator of CDRE-driven transcription. Crz1p contains zinc finger motifs and binds specifically to the CDRE. Genetic analysis revealed that crz1Delta mutant cells exhibit several phenotypes similar to those of calcineurin mutants and that overexpression of CRZ1 in calcineurin mutants suppressed these phenotypes. These results suggest that Crz1p functions downstream of calcineurin to effect multiple calcineurin-dependent responses. Moreover, the calcineurin-dependent transcriptional induction of FKS2 in response to Ca2+, alpha-factor, and Na+ was found to require CRZ1. In addition, we found that the calcineurin-dependent transcriptional regulation of PMR2 and PMC1 required CRZ1. However, transcription of PMR2 and PMC1 was activated by only a subset of the treatments that activated FKS2 transcription. Thus, in response to multiple signals, calcineurin acts through the Crz1p transcription factor to differentially regulate the expression of several target genes in yeast.

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In S. cerevisiae, expression of FKS2 is regulated by both PKC signaling and calcineurin.
“In S. cerevisiae, expression of one of the two partially redundant genes encoding the essential (1,3)-β-D-glucan synthase activity, FKS2, is regulated by both PKC signaling and calcineurin [46],[47].”
From Hsp90 Governs Echinocandin Resistance in the Pathogenic Yeast Candida albicans via Calcineurin (2009) · cites this paper as [46]
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 Stathopoulos and Cyert 1997
Crz1p binds to the CDRE sequence in FKS2 and ENA1 promoters and activates expression of calcineurin-responsive genes.
“To drive this transcriptional stress response, Crz1p binds to a cognate sequence called CDRE, already identified in FKS2 and ENA1 gene promoters, and activates the expression of calcineurin-responsive genes (Stathopoulos and Cyert 1997;Mendizabal et al. 2001).”
From Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor (2005) · cites this paper as Stathopoulos and Cyert 1997

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Authors: Stathopoulos, A. M., & Cyert, M. S.
Affiliations: Stanford University (US)
ORCID: Stathopoulos, Angelike M.
Cyert, Martha S.
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 1997-12-15
Volume: 11
Issue: 24
Pages: 3432-3444
ISSN: 0890-9369 (ISSN-L)
1549-5477
DOI: 10.1101/gad.11.24.3432
PMC: PMC316814
OpenAlex: W2132723128
Cited by: 442
References: 60
Citations by year: 2026: 7 · 2025: 11 · 2024: 7 · 2023: 9 · 2022: 15 · 2021: 13 · 2020: 16 · 2019: 13 · 2018: 12 · 2017: 17 · 2016: 21 · 2015: 12 · 2014: 22 · 2013: 17 · 2012: 18
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Genes & Development (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
CaltechAUTHORS (California Institute of Technology) (submittedVersion, cc-by-nc)
HighWire Press Open Archive (submittedVersion)
Funders: National Science Foundation (9357017)
Procter and Gamble
National Institutes of Health
National Institute of General Medical Sciences (5T32 GM07276-22, GM-48729, T32GM007276, R01GM048729)
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, Crz1, TCN1, transcription factors, Ca2+/calmodulin signaling, FKS2, beta-1,3-glucan synthase, transcriptional activation, alpha-factor, sodium, Saccharomyces cerevisiae, zinc finger, gene expression regulation
MeSH terms: Amino Acid Sequence, DNA-Binding Proteins, Glucosyltransferases, Membrane Proteins, Molecular Sequence Data, Mutation, Phenotype, Plasmids, Saccharomyces cerevisiae, Transcription Factors, Transcription, Genetic, Trans-Activators, Gene Expression Regulation, Fungal, Genes, Reporter, Calcineurin, Saccharomyces cerevisiae Proteins

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Calcineurin acts through the CRZ1/TCN1-encoded transcription factor to regulate gene expression in yeast

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