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Department of Biology, Johns Hopkins University,
Baltimore, Maryland 21218 USA
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.
[Key Words: Calcineurin; transcription; signal transduction; calcium]
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