The bZip transcription factor Cgap1p is involved in multidrug resistance and required for activation of multidrug transporter gene CgFLR1 in Candida glabrata

Kuang Hua Chen, Taiga Miyazaki, Huei Fung Tsai, John E. Bennett

Research output: Contribution to journalArticlepeer-review

Abstract

Transcriptional regulation in response to environmental challenges is crucial for survival of many organisms. In this study, we characterized structural and functional properties of CgAP1, a Saccharomyces cerevisiae YAP1 ortholog, which encodes a transcription factor involved in various stress responses. Deletion of CgAP1 led to decreased resistance to hydrogen peroxide, 4-nitroquinoline-N-oxide (4-NQO), benomyl, and cadmium chloride, which could be fully recovered by reintroduction of an intact CgAP1. CgAP1 was shown to function in S. cerevisiae as it restored the drug resistance of the yap1 mutant. Moreover, overexpression of CgAP1 in a S. cerevisiae wild-type strain increased its resistance to cycloheximide, 1,10-phenanthroline, 4-NQO, and fluconazole. Overexpression of CgAP1 also phenotypically suppressed the drug sensitivity of two Yap1p-regulated transporter mutants, Δatr1 and Δflr1, to diamide, 4-NQO, and cadmium. Northern blot analysis indicated that Cgap1p regulates the benomyl-induced expression of CgFLR1, a homolog of S. cerevisiae FLR1, which encodes a transporter of the major facilitator superfamily. In contrast to the S. cerevisiae flr1 mutant, deletion of CgFLR1 in C. glabrata only resulted in increased sensitivity to benomyl, diamide, and menadione, but not 4-NQO, cycloheximide, or fluconazole. Taken together, this report demonstrated that CgAP1 plays a critical role in response to various stresses in C. glabrata and reduces the stress through transcriptional activation of its target genes including CgFLR1.

Original languageEnglish (US)
Pages (from-to)63-72
Number of pages10
JournalGene
Volume386
Issue number1-2
DOIs
StatePublished - Jan 15 2007

Keywords

  • Benomyl
  • FLR1
  • Stress response
  • YAP1
  • Yeast

ASJC Scopus subject areas

  • Genetics

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