{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:07:20Z","timestamp":1784725640331,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T00:00:00Z","timestamp":1518393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM49825"],"award-info":[{"award-number":["GM49825"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Resistance to azole drugs, the major clinical antifungal compounds, is most commonly due to gain\u2010of\u2010function (GOF) substitution mutations in a gene called <jats:italic>PDR1<\/jats:italic> in the fungal pathogen <jats:italic>Candida glabrata<\/jats:italic>. <jats:italic>PDR1<\/jats:italic> encodes a zinc cluster\u2010containing transcription factor. GOF forms of Pdr1 drive high level expression of downstream target gene expression with accompanying azole resistance. <jats:italic>PDR1<\/jats:italic> has two homologous genes in <jats:italic>Saccharomyces cerevisiae<\/jats:italic>, called Sc<jats:italic>PDR1<\/jats:italic> and Sc<jats:italic>PDR3<\/jats:italic>. This study provides evidence that the <jats:italic>PDR1<\/jats:italic> gene in <jats:italic>C. glabrata<\/jats:italic> represents a blend of the properties found in the two <jats:italic>S. cerevisiae<\/jats:italic> genes. We demonstrated that GOF Pdr1 derivatives are overproduced at the protein level and less stable than the wild\u2010type protein. Overproduction of wild\u2010type Pdr1 increased target gene expression but to a lesser extent than GOF derivatives. Site\u2010directed mutagenesis of Pdr1 binding sites in the <jats:italic>PDR1<\/jats:italic> promoter provided clear demonstration that autoregulation of <jats:italic>PDR1<\/jats:italic> is required for its normal function. An internal deletion mutant of Pdr1 lacking its central regulatory domain behaved as a hyperactive transcription factor that was lethal unless conditionally expressed. A full understanding of the regulation of Pdr1 will provide a new avenue of interfering with azole resistance in <jats:italic>C.\u00a0glabrata<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/mmi.13913","type":"journal-article","created":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T13:12:55Z","timestamp":1516799575000},"page":"747-764","source":"Crossref","is-referenced-by-count":36,"title":["Positive autoregulation and repression of transactivation are key regulatory features of the <i>Candida glabrata<\/i> Pdr1 transcription factor"],"prefix":"10.1111","volume":"107","author":[{"given":"Svetlana","family":"Khakhina","sequence":"first","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Carver College of Medicine University of Iowa Iowa City IA 52242 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Simonicova","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Carver College of Medicine University of Iowa Iowa City IA 52242 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7163-1120","authenticated-orcid":false,"given":"W. 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