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Mol. Cells 2003; 15(1): 55-61

Published online February 28, 2003

© The Korean Society for Molecular and Cellular Biology

The Possible Mechanism of Action of Ciclopirox Olamine in the Yeast Saccharomyces cerevisiae

Sun-Hee Leem, Jung-Eun Park, Il-Shin Kim, Ji-Youn Chae, Akio Sugino, Yangil Sunwoo

Abstract

Ciclopirox olamine is a synthetic antifungal agent with a high affinity for trivalent metal cations. Ciclopirox olamine can be used to synchronize mammalian cells, but its mechanism of action is not understood well. In this study, we investigated the effect of ciclopirox olamine in yeast cells and used a genetic approach to identify potential ciclopirox olamine targets in yeast. Wild type strains of the yeast Saccharomyces cerevisiae were weakly sensitive to ciclopirox olamine, but high concentrations of the drug arrested their growth at many different stages. MMS-mutagenized yeast clones were screened for increased sensitivity to ciclopirox olamine. Fourteen mutants, cos101-cos114, were identified and characterized. The targets of ciclopirox olamine in S. cerevisiae appear to include multiple proteins that participate in various components of cellular metabolism, including DNA replication, DNA repair, and cellular transport. Three genes were cloned: a Fe/Cu reductase (FRE1/COS107), an oxidative stress response gene (YAP1/COS110), and a gene involved in signal transduction (YBR203W/COS111). These results suggest that CPO inhibits multiple aspects of cell growth and metabolism, possibly via multiple targets.

Keywords FRE1/COS107, YAP1/COS110, YBR203W/COS111, cos (circlopirox olamine sensitivity) Mutant, Ciclopirox Olamine

Article

Research Article

Mol. Cells 2003; 15(1): 55-61

Published online February 28, 2003

Copyright © The Korean Society for Molecular and Cellular Biology.

The Possible Mechanism of Action of Ciclopirox Olamine in the Yeast Saccharomyces cerevisiae

Sun-Hee Leem, Jung-Eun Park, Il-Shin Kim, Ji-Youn Chae, Akio Sugino, Yangil Sunwoo

Abstract

Ciclopirox olamine is a synthetic antifungal agent with a high affinity for trivalent metal cations. Ciclopirox olamine can be used to synchronize mammalian cells, but its mechanism of action is not understood well. In this study, we investigated the effect of ciclopirox olamine in yeast cells and used a genetic approach to identify potential ciclopirox olamine targets in yeast. Wild type strains of the yeast Saccharomyces cerevisiae were weakly sensitive to ciclopirox olamine, but high concentrations of the drug arrested their growth at many different stages. MMS-mutagenized yeast clones were screened for increased sensitivity to ciclopirox olamine. Fourteen mutants, cos101-cos114, were identified and characterized. The targets of ciclopirox olamine in S. cerevisiae appear to include multiple proteins that participate in various components of cellular metabolism, including DNA replication, DNA repair, and cellular transport. Three genes were cloned: a Fe/Cu reductase (FRE1/COS107), an oxidative stress response gene (YAP1/COS110), and a gene involved in signal transduction (YBR203W/COS111). These results suggest that CPO inhibits multiple aspects of cell growth and metabolism, possibly via multiple targets.

Keywords: FRE1/COS107, YAP1/COS110, YBR203W/COS111, cos (circlopirox olamine sensitivity) Mutant, Ciclopirox Olamine

Mol. Cells
Sep 30, 2021 Vol.44 No.9, pp. 627~698
COVER PICTURE
Non-mitochondrial localization of the N-terminal-deleted mutant form of ACSL1 in Cos7 cells. Green, ACSL1 mutant; Red, mitotracker; Blue, DAPI (Nan et al., pp. 637-646).

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