CDR1, a multidrug resistance gene from Candida albicans, contains multipleregulatory domains in its promoter and the distal AP-1 element mediates its induction by miconazole

We previously demonstrated that the CDR1 gene, encoding a multidrug transpo rter in Candida albicans, is differentially upregulated by various drugs an d steroids. In order to get an insight into the molecular basis of the indu ction of this gene we analyzed its promoter region. The transcription start site was mapped to 63 nucleotides upstream of the initiating ATG. Reporter assays revealed the presence of four upstream activating and four upstream repressing sequence domains along the entire promoter. Like the native gen e, promoter-luciferase recombinants showed enhanced activity in response to various stresses like drugs, human steroid hormones and heavy metals. Muta tional analysis demonstrated that while the proximal promoter (-345/+1) con tains all the regulatory domains required for its induction by various othe r stresses, the miconazole response is mediated via the distal promoter (-8 57/-1147), harboring an AP-1 site. The involvement of the AP-1 element in m ediating the latter effect was evident by an increase in AP-1 binding activ ity following miconazole treatment. (C) 1999 Federation of European Microbi ological Societies. Published by Elsevier Science B.V. All rights reserved.