Abstract: In the course of our screening program for a new inhibitor of the Ca(2+) -signaling pathway using mutant yeast (Saccharomyces cerevisiae (zds1Delta erg3Delta pdr1Delta pdr3Delta)), a mouse PP2Calpha activator, pisiferdiol, isolated from Chamaecyparis pisifera, was found to alleviate the Ca(2+) -signal-mediated growth inhibition. Pisiferdiol showed growth inhibition activity against the mpk1Delta strain compared to the cnb1Delta strain and induced Li(+) -sensitivity to the wild type strain, indicating that it suppresses the calcineurin pathway in the yeast. However the Li(+) -sensitivity to ptc1Delta strain by pisiferdiol was diminished. Pisiferdiol showed growth restored activity in the zds1Delta strain without immunophilins Fkb1p or Cph1p, and in the pmc1Delta strain. It inhibited calcineurin induced expression in the reporter gene assay and decreased the protein expression (Western blots) of calcineurin (Cnb1p) in addition to a decrease of Swe1p and phosphorylation of Cdc28p in the mutant yeast. These results showed that pisiferdiol could suppress indirectly the action of calcineurin and restored the growth inhibition of the mutant yeast through Ptc1p activation. (c) 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.CI - (c) 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.