AP1-mediated Multidrug Resistance in Saccharomyces cerevisiae Requires FLR1 Encoding a Transporter of the Major Facilitator Superfamily

摘要: We have isolated a Candida albicans gene that confers resistance to the azole derivative fluconazole (FCZ) when overexpressed in Saccharomyces cerevisiae. This encodes protein highly homologous S. cerevisiae yAP-1, bZip transcription factor known mediate cellular toxicants such as cycloheximide (CYH), 4-nitroquinoline N-oxide (4-NQO), cadmium, and hydrogen peroxide. The was named CAP1, for C. AP-1. Cap1 yAP-1 are functional homologues, since CAP1 expression yap1 mutant strain partially restores ability of cells grow on toxic concentrations cadmium or found YBR008c, an open reading frame identified yeast genome sequencing project predicted code multidrug transporter major facilitator superfamily, is dramatically induced overexpressing CAP1. Overexpression either YAP1 wild-type results FCZ, CYH, 4-NQO, whereas completely abrogated (FCZ CYH) strongly reduced (4-NQO) ybr008c deletion mutant, demonstrating YBR008c involved YAP1- CAP1-mediated resistance. has been renamed FLR1, 1. FLR1-lacZ reporter construct by overexpression YAP1, indicating FLR1 transcriptionally regulated proteins. Taken collectively, our demonstrate represents new YAP1-controlled molecular determinant A similar detoxification pathway also likely operate albicans.