Inhibition of Ca²⁺-Signal-Dependent Growth Regulation by Radicicol in Budding Yeast

Abstract

Compelled activation of Ca²⁺ signaling by exposure of zds1Δ strain Saccharomyces cerevisiae cells to external CaCl₂ leads to characteristic physiological consequences such as growth inhibition in the G₂ phase and polarized bud growth. Screening of microbial metabolites for activity alleviating the deleterious physiological effects of external CaCl₂ identified the Hsp90 inhibitor radicicol as an inhibitor of Ca²⁺-signal-dependent cell-cycle regulation in yeast. Radicicol alleviated analogous physiological effects due to the expression of a constitutively active form of calcineurin or overexpression of Swe1, the negative regulatory kinase of the Cdc28-Clb complex. Western blot analysis indicated that radicicol inhibited Ca²⁺-induced accumulation of Swe1 and Cln2.