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

• First, CRZ1 was not involved in tolerance to antifungal agents (fluconazole, terbinafine) on the opposite to calcineurin [8].
• Cells deleted for CRZ1 or treated with the calcineurin inhibitor FK506 became hypersensitive to chitosan, supporting the notion that the Crz1p-controlled response offers protection against chitosan [9].
• Moreover, MG activated the uptake of Ca(2+) in yeast cells, thereby stimulating the calcineurin/Crz1-mediated Ca(2+) signaling pathway [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 [10].
• Distinct regulatory mechanism of yeast GPX2 encoding phospholipid hydroperoxide glutathione peroxidase by oxidative stress and a calcineurin/Crz1-mediated Ca2+ signaling pathway [11].

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

• We used DNA microarrays to perform a comprehensive analysis of calcineurin/Crz1p-dependent gene expression following addition of Ca(2+) (200 mm) or Na(+) (0.8 m) to yeast [17].

References