title: Pisiferdiol restores the growth of a mutant yeast suffering from hyperactivated Ca2+ signalling through calcineurin inhibition.
abstract: In the course of our screening program for a new inhibitor of the Ca(2+)  signalling pathway using mutant yeast [Saccharomyces cerevisiae (zds1Δ erg3Δ pdr1Δ pdr3Δ)], a mouse PP2Cα activator, pisiferdiol, isolated from Chamaecyparis pisifera, was found to alleviate the Ca(2+)  signal-mediated growth inhibition. Pisiferdiol showed growth inhibition activity against the mpk1Δ strain compared with the cnb1Δ 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 ptc1Δ strain by pisiferdiol was diminished. Pisiferdiol showed growth restored activity in the zds1Δ strain without immunophilins Fkb1p or Cph1p, and in the pmc1Δ 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.
authors.affiliation: The United Graduate School of Agricultural Sciences, Iwate University, Morioka, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Aburai
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshida
authors.forename: Miki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Masaki
authors.initials: M
authors.lastname: Mizunuma
authors.forename: Motoko
authors.initials: M
authors.lastname: Ohnishi
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kimura
mesh_terms: D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D020013:Calcium Signaling / Q000187:drug effects*; D029780:Chamaecyparis / Q000737:chemistry; D004224:Diterpenes / Q000494:pharmacology*; D020536:Enzyme Activators / Q000494:pharmacology; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D020104:Immunophilins / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D000071636:Protein Phosphatase 2C; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013315:Stress, Psychological
chemical_list: D065095:Calcineurin Inhibitors; D004224:Diterpenes; D020536:Enzyme Activators; D010936:Plant Extracts; D029701:Saccharomyces cerevisiae Proteins; C060710:pisiferic acid; D008094:Lithium; D019703:Calcineurin; C087358:PTC1 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D000071636:Protein Phosphatase 2C; D020104:Immunophilins