{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T13:46:44Z","timestamp":1765806404205},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,2,10]],"date-time":"2004-02-10T00:00:00Z","timestamp":1076371200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Yeast"],"published-print":{"date-parts":[[2004,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>CDR1<\/jats:italic> gene encoding an ATP\u2010driven drug extrusion pump has been implicated in the development of azole\u2010resistance in <jats:italic>Candida albicans<\/jats:italic>. Although the upregulation of <jats:italic>CDR1<\/jats:italic> expression by various environmental factors has been documented, the molecular mechanism underlying such process is poorly understood. We have demonstrated earlier that the <jats:italic>CDR1<\/jats:italic> promoter encompasses a large number of <jats:italic>cis<\/jats:italic>\u2010regulatory elements, presumably mediating its response to various drugs. In this study we have identified a novel steroid responsive region (SRR) conferring \u03b2\u2010oestradiol and progesterone inducibility on the <jats:italic>CDR1<\/jats:italic> promoter. The SRR is located \u2212696 to \u2212521 <jats:italic>bp<\/jats:italic> upstream of the transcription start site; it is modular in nature and can confer steroid responsiveness to a heterologous promoter (<jats:italic>ADH1<\/jats:italic>) linked to a <jats:italic>GFP<\/jats:italic> reporter gene. <jats:italic>In vitro<\/jats:italic> DNase I protection analyses of SRR revealed two progesterone responsive sequences (\u2212628 to \u2212594 and \u2212683 to \u2212648) and one \u03b2\u2010oestradiol responsive sequence (\u2212628 to \u2212577), which was further corroborated by the gel mobility shift assay. Deletion analyses within the SRR further delimited these steroid responsive sequences into two distinct elements, viz. SRE1 and SRE2. While SRE1 (\u2212677 to \u2212648) responds only to progesterone, SRE2 (\u2212628 to \u2212598) responded to both progesterone and \u03b2\u2010oestradiol. Both SRE1 and SRE2 were specific for steroids, as they did not respond to other drugs, such as cycloheximide, miconazole and terbinafine. <jats:italic>In silico<\/jats:italic> comparison of the SRE1\/2 with the promoter sequences of other MDR (<jats:italic>CDR2<\/jats:italic> and <jats:italic>PDR5<\/jats:italic>) and non\u2010MDR (<jats:italic>HSP90<\/jats:italic>) steroid\u2010responsive genes revealed a similarity with respect to conservation of three 5 bp stretches (AAGAA, CCGAA and ATTGG). Taken together, we have identified a novel steroid responsive <jats:italic>cis<\/jats:italic>\u2010regulatory sequence in the <jats:italic>CDR1<\/jats:italic> promoter, which presumably can be instrumental in understanding the steroid response cascade in <jats:italic>Candida albicans.<\/jats:italic> Copyright \u00a9 2004 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/yea.1067","type":"journal-article","created":{"date-parts":[[2004,2,12]],"date-time":"2004-02-12T08:01:59Z","timestamp":1076572919000},"page":"219-239","source":"Crossref","is-referenced-by-count":51,"title":["SRE1 and SRE2 are two specific steroid\u2010responsive modules of <i>Candida<\/i> drug resistance gene 1 (<i>CDR1<\/i>) promoter"],"prefix":"10.1002","volume":"21","author":[{"given":"Neerja","family":"Karnani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naseem 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