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
A. Shitamukai et al., 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, BIOS BIOT B, 64(9), 2000, pp. 1942-1946
An inappropriate activation of a signaling pathway in yeast often has a del
eterious physiological effect and causes various defects, including growth
defects. In a certain genetic background (Delta zds1) of Saccharomyces cere
visiae, the cell-cycle progression in G2 is specifically blocked in the med
ium with CaCl2 by the hyperactivation of the Ca2+-signaling pathways. Here,
we developed a novel drug screening procedure designed to detect the activ
e compounds that specifically attenuate the Ca2+-signaling activity on the
basis of the ability to abrogate the growth defect of the cells suffering f
rom the hyperactivated Ca2+ signal. Using known calcineurin inhibitors as m
odel 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 mutatio
n.