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

Genes Dev. 1997 Dec 15;11(24):3445-58. doi: 10.1101/gad.11.24.3445.

Abstract

Ca2+ signals regulate gene expression in animal and yeast cells through mechanisms involving calcineurin, a protein phosphatase activated by binding Ca2+ 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 Ca2+, Mn2+, Na+, and cell wall damage, respectively. Tcn1p was not required for other calcineurin-dependent processes, such as inhibition of a vacuolar H+/Ca2+ exchanger and inhibition of a pheromone-stimulated Ca2+ 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 Ca2+-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 Ca2+ signals generated by treatment with mating pheromone and high salt. We propose that different promoters are sensitive to variations in the strength of Ca2+ signals generated by these stimuli and to effects of other signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Calcineurin / metabolism*
  • Calcium / metabolism
  • Calcium-Transporting ATPases / genetics
  • Calcium-Transporting ATPases / metabolism
  • DNA-Binding Proteins
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Expression Regulation, Fungal*
  • Genes, Reporter
  • Glucosyltransferases*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • Pheromones / pharmacology
  • Plasma Membrane Calcium-Transporting ATPases
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins*
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism*
  • Transcription Factors / drug effects
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • beta-Galactosidase / genetics
  • beta-Galactosidase / metabolism

Substances

  • CRZ1 protein, S cerevisiae
  • DNA-Binding Proteins
  • Fungal Proteins
  • Membrane Proteins
  • PMC1 protein, S cerevisiae
  • Pheromones
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Transcription Factors
  • Glucosyltransferases
  • GSC2 protein, S cerevisiae
  • Calcineurin
  • beta-Galactosidase
  • Plasma Membrane Calcium-Transporting ATPases
  • Calcium-Transporting ATPases
  • Calcium