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Gene Review

CRZ1  -  Crz1p

Saccharomyces cerevisiae S288c

Synonyms: HAL8, N2760, TCN1, Transcriptional regulator CRZ1, YNL027W
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High impact information on CRZ1

  • Calcineurin promotes cell survival during stress by dephosphorylating and activating the Zn-finger transcription factor Crz1p/Tcn1p [1].
  • In addition, we define the Crz1p nuclear export signal (NES) and show that it interacts with Msn5p in a phosphorylation-dependent manner [2].
  • Using a genetic approach, we identify Msn5p as the exportin for Crz1p [2].
  • In this work, we show that calcineurin-dependent dephosphorylation of Crz1p also down-regulates its nuclear export [2].
  • In the yeast, Saccharomyces cerevisiae, calcineurin effects Ca2+-dependent changes in gene expression through regulation of the Crz1p transcription factor [3].

Biological context of CRZ1

  • 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 [4].
  • Calcineurin acts through the CRZ1/TCN1-encoded transcription factor to regulate gene expression in yeast [4].
  • Crz1p contains zinc finger motifs and binds specifically to the CDRE [4].
  • 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 [5].
  • 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 [5].

Anatomical context of CRZ1

  • Pmc1p, the Ca(2+)-ATPase of budding yeast related to plasma membrane Ca(2+)-ATPases of animals, is transcriptionally up-regulated in response to signaling by the calmodulin-calcineurin-Tcn1p/Crz1p signaling pathway [6].
  • Calcineurin dephosphorylates Crz1p and causes its rapid translocation from the cytosol to the nucleus [7].

Associations of CRZ1 with chemical compounds


Physical interactions of CRZ1

  • The DNA-binding domain of Skn7p is also required for binding to Crz1p and calcineurin in vitro [12].

Regulatory relationships of CRZ1

  • The eukaryotic response regulator Skn7p regulates calcineurin signaling through stabilization of Crz1p [12].
  • We have investigated the molecular mechanisms involved in ENA1 induction by the calcium-calcineurin-activated transcription factor Crzl/Tcn1 [13].

Other interactions of CRZ1

  • Expression analysis of Cka2p-responsive genes argues that Cka2p and Crz1p act through distinct mechanisms [14].
  • This motif is related to calcineurin docking sites in other substrates, such as NFAT and Crz1p, and is required for regulation of Hph1p by calcineurin [15].
  • Moreover, the calcineurin-dependent transcriptional induction of FKS2 in response to Ca2+, alpha-factor, and Na+ was found to require CRZ1 [4].
  • Tcn1p contains three zinc finger motifs at its carboxyl terminus resembling the DNA-binding domains of Zif268, Swi5p, and other transcription factors [5].
  • Hal8p seems to mediate the calcineurin-dependent part of ENA1 expression [16].

Analytical, diagnostic and therapeutic context of CRZ1


  1. Negative regulation of calcineurin signaling by Hrr25p, a yeast homolog of casein kinase I. Kafadar, K.A., Zhu, H., Snyder, M., Cyert, M.S. Genes Dev. (2003) [Pubmed]
  2. Calcineurin-dependent regulation of Crz1p nuclear export requires Msn5p and a conserved calcineurin docking site. Boustany, L.M., Cyert, M.S. Genes Dev. (2002) [Pubmed]
  3. Yeast calcineurin regulates nuclear localization of the Crz1p transcription factor through dephosphorylation. Stathopoulos-Gerontides, A., Guo, J.J., Cyert, M.S. Genes Dev. (1999) [Pubmed]
  4. Calcineurin acts through the CRZ1/TCN1-encoded transcription factor to regulate gene expression in yeast. Stathopoulos, A.M., Cyert, M.S. Genes Dev. (1997) [Pubmed]
  5. Tcn1p/Crz1p, a calcineurin-dependent transcription factor that differentially regulates gene expression in Saccharomyces cerevisiae. Matheos, D.P., Kingsbury, T.J., Ahsan, U.S., Cunningham, K.W. Genes Dev. (1997) [Pubmed]
  6. Inhibition of the Ca(2+)-ATPase Pmc1p by the v-SNARE protein Nyv1p. Takita, Y., Engstrom, L., Ungermann, C., Cunningham, K.W. J. Biol. Chem. (2001) [Pubmed]
  7. Calcineurin signaling in Saccharomyces cerevisiae: how yeast go crazy in response to stress. Cyert, M.S. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  8. CRZ1, a target of the calcineurin pathway in Candida albicans. Karababa, M., Valentino, E., Pardini, G., Coste, A.T., Bille, J., Sanglard, D. Mol. Microbiol. (2006) [Pubmed]
  9. Transcriptional response of Saccharomyces cerevisiae to the plasma membrane-perturbing compound chitosan. Zakrzewska, A., Boorsma, A., Brul, S., Hellingwerf, K.J., Klis, F.M. Eukaryotic Cell (2005) [Pubmed]
  10. Methylglyoxal, a metabolite derived from glycolysis, functions as a signal initiator of the high osmolarity glycerol-mitogen-activated protein kinase cascade and calcineurin/Crz1-mediated pathway in Saccharomyces cerevisiae. Maeta, K., Izawa, S., Inoue, Y. J. Biol. Chem. (2005) [Pubmed]
  11. Distinct regulatory mechanism of yeast GPX2 encoding phospholipid hydroperoxide glutathione peroxidase by oxidative stress and a calcineurin/Crz1-mediated Ca2+ signaling pathway. Tsuzi, D., Maeta, K., Takatsume, Y., Izawa, S., Inoue, Y. FEBS Lett. (2004) [Pubmed]
  12. The eukaryotic response regulator Skn7p regulates calcineurin signaling through stabilization of Crz1p. Williams, K.E., Cyert, M.S. EMBO J. (2001) [Pubmed]
  13. Promoter sequences regulated by the calcineurin-activated transcription factor Crz1 in the yeast ENA1 gene. Mendizabal, I., Pascual-Ahuir, A., Serrano, R., de Larrinoa, I.F. Mol. Genet. Genomics (2001) [Pubmed]
  14. Regulation of azole drug susceptibility by Candida albicans protein kinase CK2. Bruno, V.M., Mitchell, A.P. Mol. Microbiol. (2005) [Pubmed]
  15. Hph1p and Hph2p, novel components of calcineurin-mediated stress responses in Saccharomyces cerevisiae. Heath, V.L., Shaw, S.L., Roy, S., Cyert, M.S. Eukaryotic Cell (2004) [Pubmed]
  16. Yeast putative transcription factors involved in salt tolerance. Mendizabal, I., Rios, G., Mulet, J.M., Serrano, R., de Larrinoa, I.F. FEBS Lett. (1998) [Pubmed]
  17. Genome-wide analysis of gene expression regulated by the calcineurin/Crz1p signaling pathway in Saccharomyces cerevisiae. Yoshimoto, H., Saltsman, K., Gasch, A.P., Li, H.X., Ogawa, N., Botstein, D., Brown, P.O., Cyert, M.S. J. Biol. Chem. (2002) [Pubmed]
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