A Positive Screening for Drugs that Specifically Inhibit the Ca²⁺-Signaling Activity on the Basis of the Growth Promoting Effect on a Yeast Mutant with a Peculiar Phenotype

Abstract

An inappropriate activation of a signaling pathway in yeast often has a deleterious physiological effect and causes various defects, including growth defects. In a certain genetic background (Δzds1) of Saccharomyces cerevisiae, the cell-cycle progression in G2 is specifically blocked in the medium with CaCl₂ by the hyperactivation of the Ca²⁺-signaling pathways. Here, we developed a novel drug screening procedure designed to detect the active compounds that specifically attenuate the Ca²⁺-signaling activity on the basis of the ability to abrogate the growth defect of the cells suffering from the hyperactivated Ca²⁺ signal. Using known calcineurin inhibitors as model compounds, we have established the screening conditions for the drugs that suppress the Ca²⁺-induced growth inhibition. An indicator strain with an increased drug sensitivity was constructed with a syr1/erg3 null mutation.

• Ca²⁺ signal
• calcineurin
• drug screening
• immunosuppressant
• MAP kinase