The eukaryotic response regulator Skn7p regulates calcineurin signaling through stabilization of Crz1p

To survive ionic, pH and pheromone stress, the yeast Saccharomyces cerevisiae activates signaling through the Ca2+-activated phosphatase calcineurin to the transcription factor Crz1p/Tcn1p, We show that the overexpression of SKN7, a response-regulator transcription factor, activates transcription from a calcineurin/Crz1p-dependent response element (CDRE), Ca2+-induced, calcineurin/Crz1p-dependent activation of several genes is reduced in skn7 mutants. Skn7p modulates CDRE-dependent transcription by affecting Crz1p protein levels. Specifically, the rate of Crz1p turnover is increased in skn7 mutants. Calcineurin, but not its phosphatase activity, is required for Skn7p-mediated Crz1p stabilization. Skn7p binds to both calcineurin and Crz1p in vitro, and we suggest that this interaction is required for Skn7p regulation of Crz1p, The DNA-binding and internal coiled-coil domains, but not the response-regulator phosphorylation of Skn7p, are necessary for Crz1p-dependent transcriptional activation and Crz1p stabilization by Skn7 in vivo. The DNA-binding domain of Skn7p is also required for binding to Crz1p and calcineurin in vitro. Thus, we propose that Skn7p protects Crz1p from degradation by binding to it and calcineurin through its DNA-binding domain.