{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:07:00Z","timestamp":1784725620817,"version":"3.55.0"},"reference-count":59,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,9,30]],"date-time":"2018-09-30T00:00:00Z","timestamp":1538265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The primary route for development of azole resistance in the fungal pathogen <jats:italic>Candida glabrata<\/jats:italic> is acquisition of a point mutation in the <jats:italic>PDR1<\/jats:italic> gene. This locus encodes a transcription factor that upon mutation drives high level expression of a range of genes including the ATP\u2010binding cassette transporter\u2010encoding gene <jats:italic>CDR1<\/jats:italic>. Pdr1 activity is also elevated in cells that lack the mitochondrial genome (\u03c1<jats:sup>\u00b0<\/jats:sup> cells), with associated high expression of <jats:italic>CDR1<\/jats:italic> driving azole resistance. To gain insight into the mechanisms controlling activity of Pdr1, we expressed a tandem affinity purification (TAP)\u2010tagged form of Pdr1 in both wild\u2010type (\u03c1<jats:sup>+<\/jats:sup>) and \u03c1<jats:sup>\u00b0<\/jats:sup> cells. Purified proteins were analyzed by multidimensional protein identification technology mass spectrometry identifying a protein called Bre5 as a factor that co\u2010purified with TAP\u2010Pdr1. In <jats:italic>Saccharomyces cerevisiae<\/jats:italic>, Bre5 is part of a deubiquitinase complex formed by association with the ubiquitin\u2010specific protease Ubp3. Genetic analyses in <jats:italic>C. glabrata<\/jats:italic> revealed that loss of <jats:italic>BRE5<\/jats:italic>, but not <jats:italic>UBP3<\/jats:italic>, led to an increase in expression of <jats:italic>PDR1<\/jats:italic> and <jats:italic>CDR1<\/jats:italic> at the transcriptional level. These studies support the view that Bre5 acts as a negative regulator of Pdr1 transcriptional activity and behaves as a <jats:italic>C. glabrata<\/jats:italic>\u2010specific modulator of azole resistance.<\/jats:p>","DOI":"10.1111\/mmi.14109","type":"journal-article","created":{"date-parts":[[2018,8,23]],"date-time":"2018-08-23T15:19:00Z","timestamp":1535037540000},"page":"309-323","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Negative regulation of <i>Candida glabrata<\/i> Pdr1 by the deubiquitinase subunit Bre5 occurs in a ubiquitin independent manner"],"prefix":"10.1111","volume":"110","author":[{"given":"Sanjoy","family":"Paul","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":"W. 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