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.
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 (deltazds1) 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.
Shitamukai
A
A
Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan.
Mizunuma
M
M
Hirata
D
D
Takahashi
H
H
Miyakawa
T
T
D065095:Calcineurin Inhibitors; D002122:Calcium Chloride / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D016572:Cyclosporine / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D016195:G2 Phase; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012680:Sensitivity and Specificity; D016559:Tacrolimus / Q000494:pharmacology*
D065095:Calcineurin Inhibitors; D016572:Cyclosporine; D002122:Calcium Chloride; D016559:Tacrolimus