title: Transcription factors CgUPC2A and CgUPC2B regulate ergosterol biosynthetic genes in Candida glabrata.
abstract: 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 (upc2AΔ) exhibited enhanced susceptibility to the sterol biosynthesis inhibitors, fluconazole and lovastatin, whereas upc2BΔ-mutant cells were as susceptible to the drugs as wild-type cells. The growth of upc2AΔ cells was also severely attenuated under anaerobic conditions. Lovastatin treatment enhanced the expression of ergosterol biosynthetic genes, ERG2 and ERG3 in wild-type and upc2BΔ but not in upc2AΔ cells. Similarly, serum-induced expression of ERG2 and ERG3 was completely impaired in upc2AΔ cells but was unaffected in upc2BΔ cells, whereas serum-induced expression of the sterol transporter gene CgAUS1 was impaired in both upc2AΔ and upc2BΔ 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.
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-Ku, Tokyo 162-8640, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Nagi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Nakayama
authors.forename: Koichi
authors.initials: K
authors.lastname: Tanabe
authors.forename: Martin
authors.initials: M
authors.lastname: Bard
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Aoyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Okano
authors.forename: Satoru
authors.initials: S
authors.lastname: Higashi
authors.forename: Keigo
authors.initials: K
authors.lastname: Ueno
authors.forename: Hiroji
authors.initials: H
authors.lastname: Chibana
authors.forename: Masakazu
authors.initials: M
authors.lastname: Niimi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamagoe
authors.forename: Takashi
authors.initials: T
authors.lastname: Umeyama
authors.forename: Susumu
authors.initials: S
authors.lastname: Kajiwara
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ohno
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Miyazaki
mesh_terms: D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology; D041221:Candida glabrata / Q000235:genetics / Q000378:metabolism*; D004875:Ergosterol / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D015725:Fluconazole / Q000378:metabolism / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal / Q000187:drug effects; D008148:Lovastatin / Q000378:metabolism / Q000494:pharmacology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D013261:Sterols / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D000935:Antifungal Agents; C465208:ECM22 protein, S cerevisiae; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D013261:Sterols; D015534:Trans-Activators; D014157:Transcription Factors; C113958:UPC2 protein, S cerevisiae; D015725:Fluconazole; D008148:Lovastatin; D004875:Ergosterol