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Transcription factors CgUPC2A and CgUPC2B regulate ergosterol biosynthetic genes in Candida glabrata
Author(s) -
Nagi Minoru,
Nakayama Hironobu,
Tanabe Koichi,
Bard Martin,
Aoyama Toshihiro,
Okano Makoto,
Higashi Satoru,
Ueno Keigo,
Chibana Hiroji,
Niimi Masakazu,
Yamagoe Satoshi,
Umeyama Takashi,
Kajiwara Susumu,
Ohno Hideaki,
Miyazaki Yoshitsugu
Publication year - 2011
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2010.01470.x
Subject(s) - ergosterol , biology , sterol , mutant , candida glabrata , gene , transcription factor , saccharomyces cerevisiae , lovastatin , wild type , biochemistry , microbiology and biotechnology , cholesterol , antifungal
Zn[2]‐Cys[6] binuclear transcription factors Upc2p and Ecm22p regulate the expression of genes involved in ergosterol biosynthesis and exogenous sterol uptake in Saccharomyces cerevisiae . We identified two UPC2 / ECM22 homologues in the pathogenic fungus Candida glabrata which we designated CgUPC2A and CgUPC2B . The contribution of these two genes to sterol homeostasis was investigated. Cells that lack CgUPC2A ( upc2A Δ) exhibited enhanced susceptibility to the sterol biosynthesis inhibitors, fluconazole and lovastatin, whereas upc2B Δ‐mutant cells were as susceptible to the drugs as wild‐type cells. The growth of upc2A Δ cells was also severely attenuated under anaerobic conditions. Lovastatin treatment enhanced the expression of ergosterol biosynthetic genes, ERG2 and ERG3 in wild‐type and upc2B Δ but not in upc2A Δ cells. Similarly, serum‐induced expression of ERG2 and ERG3 was completely impaired in upc2A Δ cells but was unaffected in upc2B Δ cells, whereas serum‐induced expression of the sterol transporter gene CgAUS1 was impaired in both upc2A Δ and upc2B Δ cells. These results suggest that in C. glabrata CgUPC2A but not in CgUPC2B is the main transcriptional regulator of the genes responsible for maintaining sterol homeostasis as well as susceptibility to sterol inhibitors.