The yeast zinc finger regulators Pdr1p and Pdr3p control pleiotropic drug resistance (PDR) as homo‐ and heterodimers in vivo
Summary The transcription factors Pdr1p and Pdr3p from Saccharomyces cerevisiae mediate pleiotropic drug resistance (PDR) by controlling expression of ATP‐binding cassette (ABC) transporters such as Pdr5p, Snq2p and Yor1p. Previous in vitro studies demonstrated that Pdr1p and Pdr3p recognize so‐call...
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| Veröffentlicht in: | Molecular microbiology 2002-12, Vol.46 (5), p.1429-1440 |
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| creator | Mamnun, Yasmine M. Pandjaitan, Rudy Mahé, Yannick Delahodde, Agnés Kuchler, Karl |
| description | Summary
The transcription factors Pdr1p and Pdr3p from Saccharomyces cerevisiae mediate pleiotropic drug resistance (PDR) by controlling expression of ATP‐binding cassette (ABC) transporters such as Pdr5p, Snq2p and Yor1p. Previous in vitro studies demonstrated that Pdr1p and Pdr3p recognize so‐called pleiotropic drug resistance elements (PDREs) in the promoters of target genes. In this study, we show that both Pdr1p and Pdr3p are phosphoproteins; Pdr3p isoforms migrate as two bands in gel electrophoresis, reflecting two distinct phosphorylation states. Most importantly, native co‐immunoprecipitation experiments, using functional epitope‐tagged Pdr1p/Pdr3p variants, demonstrate that Pdr1p and Pdr3p can form both homo‐ and heterodimers in vivo. Furthermore, in vivo footprinting of PDRE‐containing promoters demonstrate that Pdr1p/Pdr3p constitutively occupy both perfect and degenerate PDREs in vivo. Thus, in addition to interaction with other regulators, differential dimerization provides a plausible explanation for the observation that Pdr3p and Pdr1p can both positively and negatively control PDR promoters with different combinations of perfect and degenerate PDREs. |
| doi_str_mv | 10.1046/j.1365-2958.2002.03262.x |
| format | Article |
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The transcription factors Pdr1p and Pdr3p from Saccharomyces cerevisiae mediate pleiotropic drug resistance (PDR) by controlling expression of ATP‐binding cassette (ABC) transporters such as Pdr5p, Snq2p and Yor1p. Previous in vitro studies demonstrated that Pdr1p and Pdr3p recognize so‐called pleiotropic drug resistance elements (PDREs) in the promoters of target genes. In this study, we show that both Pdr1p and Pdr3p are phosphoproteins; Pdr3p isoforms migrate as two bands in gel electrophoresis, reflecting two distinct phosphorylation states. Most importantly, native co‐immunoprecipitation experiments, using functional epitope‐tagged Pdr1p/Pdr3p variants, demonstrate that Pdr1p and Pdr3p can form both homo‐ and heterodimers in vivo. Furthermore, in vivo footprinting of PDRE‐containing promoters demonstrate that Pdr1p/Pdr3p constitutively occupy both perfect and degenerate PDREs in vivo. Thus, in addition to interaction with other regulators, differential dimerization provides a plausible explanation for the observation that Pdr3p and Pdr1p can both positively and negatively control PDR promoters with different combinations of perfect and degenerate PDREs.</description><identifier>ISSN: 0950-382X</identifier><identifier>EISSN: 1365-2958</identifier><identifier>DOI: 10.1046/j.1365-2958.2002.03262.x</identifier><identifier>PMID: 12453227</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>ATP-Binding Cassette Transporters - genetics ; ATP-Binding Cassette Transporters - metabolism ; Dimerization ; DNA Footprinting ; DNA-Binding Proteins - chemistry ; DNA-Binding Proteins - metabolism ; Drug Resistance, Multiple, Fungal - genetics ; Gene Expression Regulation, Fungal ; Promoter Regions, Genetic - genetics ; Saccharomyces cerevisiae - drug effects ; Saccharomyces cerevisiae - metabolism ; Saccharomyces cerevisiae Proteins ; Trans-Activators - chemistry ; Trans-Activators - metabolism ; Transcription Factors - chemistry ; Transcription Factors - metabolism ; Transcription, Genetic ; Zinc Fingers</subject><ispartof>Molecular microbiology, 2002-12, Vol.46 (5), p.1429-1440</ispartof><rights>Copyright Blackwell Scientific Publications Ltd. Dec 2002</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4892-8e3b2d9cff122d91ece7d53e5d12d826e48788ffb61aecafe6333d51e030c2d43</citedby><cites>FETCH-LOGICAL-c4892-8e3b2d9cff122d91ece7d53e5d12d826e48788ffb61aecafe6333d51e030c2d43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1365-2958.2002.03262.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1365-2958.2002.03262.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12453227$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mamnun, Yasmine M.</creatorcontrib><creatorcontrib>Pandjaitan, Rudy</creatorcontrib><creatorcontrib>Mahé, Yannick</creatorcontrib><creatorcontrib>Delahodde, Agnés</creatorcontrib><creatorcontrib>Kuchler, Karl</creatorcontrib><title>The yeast zinc finger regulators Pdr1p and Pdr3p control pleiotropic drug resistance (PDR) as homo‐ and heterodimers in vivo</title><title>Molecular microbiology</title><addtitle>Mol Microbiol</addtitle><description>Summary
The transcription factors Pdr1p and Pdr3p from Saccharomyces cerevisiae mediate pleiotropic drug resistance (PDR) by controlling expression of ATP‐binding cassette (ABC) transporters such as Pdr5p, Snq2p and Yor1p. Previous in vitro studies demonstrated that Pdr1p and Pdr3p recognize so‐called pleiotropic drug resistance elements (PDREs) in the promoters of target genes. In this study, we show that both Pdr1p and Pdr3p are phosphoproteins; Pdr3p isoforms migrate as two bands in gel electrophoresis, reflecting two distinct phosphorylation states. Most importantly, native co‐immunoprecipitation experiments, using functional epitope‐tagged Pdr1p/Pdr3p variants, demonstrate that Pdr1p and Pdr3p can form both homo‐ and heterodimers in vivo. Furthermore, in vivo footprinting of PDRE‐containing promoters demonstrate that Pdr1p/Pdr3p constitutively occupy both perfect and degenerate PDREs in vivo. Thus, in addition to interaction with other regulators, differential dimerization provides a plausible explanation for the observation that Pdr3p and Pdr1p can both positively and negatively control PDR promoters with different combinations of perfect and degenerate PDREs.</description><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>ATP-Binding Cassette Transporters - metabolism</subject><subject>Dimerization</subject><subject>DNA Footprinting</subject><subject>DNA-Binding Proteins - chemistry</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Drug Resistance, Multiple, Fungal - genetics</subject><subject>Gene Expression Regulation, Fungal</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Saccharomyces cerevisiae - drug effects</subject><subject>Saccharomyces cerevisiae - metabolism</subject><subject>Saccharomyces cerevisiae Proteins</subject><subject>Trans-Activators - chemistry</subject><subject>Trans-Activators - metabolism</subject><subject>Transcription Factors - chemistry</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic</subject><subject>Zinc Fingers</subject><issn>0950-382X</issn><issn>1365-2958</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1u1DAUhS0EokPhFZDFAsEiwT-J4yxYoPLTSq1aoSKxszz2zYxHSZzaSemwQDwCz8iT1OmMQOoGVvdI_s6RrA8hTElOSSHebHLKRZmxupQ5I4TlhDPB8psHaPHn4SFakLokGZfs6wF6EuOGEMqJ4I_RAWVFyRmrFujH5RrwFnQc8XfXG9y4fgUBB1hNrR59iPjCBjpg3ds58QEb34_Bt3howfmUBmewDdMqdaKLo-4N4FcX7z-_xjrite_875-_7uprGCF46zpIq67H1-7aP0WPGt1GeLa_h-jLxw-XR8fZ6fmnk6N3p5kpZM0yCXzJbG2ahrJ0KRiobMmhtJRZyQQUspKyaZaCajC6AcE5tyUFwolhtuCH6OVudwj-aoI4qs5FA22re_BTVBWrqGAV-ydIZcK4kAl8cQ_c-Cn06ROK1qKkghRVguQOMsHHGKBRQ3CdDltFiZpNqo2ahalZmJpNqjuT6iZVn-_3p2UH9m9xry4Bb3fAN9fC9r-H1dnZyZz4LcrErgs</recordid><startdate>200212</startdate><enddate>200212</enddate><creator>Mamnun, Yasmine M.</creator><creator>Pandjaitan, Rudy</creator><creator>Mahé, Yannick</creator><creator>Delahodde, Agnés</creator><creator>Kuchler, Karl</creator><general>Blackwell Science Ltd</general><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200212</creationdate><title>The yeast zinc finger regulators Pdr1p and Pdr3p control pleiotropic drug resistance (PDR) as homo‐ and heterodimers in vivo</title><author>Mamnun, Yasmine M. ; Pandjaitan, Rudy ; Mahé, Yannick ; Delahodde, Agnés ; Kuchler, Karl</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4892-8e3b2d9cff122d91ece7d53e5d12d826e48788ffb61aecafe6333d51e030c2d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>ATP-Binding Cassette Transporters - genetics</topic><topic>ATP-Binding Cassette Transporters - metabolism</topic><topic>Dimerization</topic><topic>DNA Footprinting</topic><topic>DNA-Binding Proteins - chemistry</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Drug Resistance, Multiple, Fungal - genetics</topic><topic>Gene Expression Regulation, Fungal</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Saccharomyces cerevisiae - drug effects</topic><topic>Saccharomyces cerevisiae - metabolism</topic><topic>Saccharomyces cerevisiae Proteins</topic><topic>Trans-Activators - chemistry</topic><topic>Trans-Activators - metabolism</topic><topic>Transcription Factors - chemistry</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription, Genetic</topic><topic>Zinc Fingers</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mamnun, Yasmine M.</creatorcontrib><creatorcontrib>Pandjaitan, Rudy</creatorcontrib><creatorcontrib>Mahé, Yannick</creatorcontrib><creatorcontrib>Delahodde, Agnés</creatorcontrib><creatorcontrib>Kuchler, Karl</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mamnun, Yasmine M.</au><au>Pandjaitan, Rudy</au><au>Mahé, Yannick</au><au>Delahodde, Agnés</au><au>Kuchler, Karl</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The yeast zinc finger regulators Pdr1p and Pdr3p control pleiotropic drug resistance (PDR) as homo‐ and heterodimers in vivo</atitle><jtitle>Molecular microbiology</jtitle><addtitle>Mol Microbiol</addtitle><date>2002-12</date><risdate>2002</risdate><volume>46</volume><issue>5</issue><spage>1429</spage><epage>1440</epage><pages>1429-1440</pages><issn>0950-382X</issn><eissn>1365-2958</eissn><abstract>Summary
The transcription factors Pdr1p and Pdr3p from Saccharomyces cerevisiae mediate pleiotropic drug resistance (PDR) by controlling expression of ATP‐binding cassette (ABC) transporters such as Pdr5p, Snq2p and Yor1p. Previous in vitro studies demonstrated that Pdr1p and Pdr3p recognize so‐called pleiotropic drug resistance elements (PDREs) in the promoters of target genes. In this study, we show that both Pdr1p and Pdr3p are phosphoproteins; Pdr3p isoforms migrate as two bands in gel electrophoresis, reflecting two distinct phosphorylation states. Most importantly, native co‐immunoprecipitation experiments, using functional epitope‐tagged Pdr1p/Pdr3p variants, demonstrate that Pdr1p and Pdr3p can form both homo‐ and heterodimers in vivo. Furthermore, in vivo footprinting of PDRE‐containing promoters demonstrate that Pdr1p/Pdr3p constitutively occupy both perfect and degenerate PDREs in vivo. Thus, in addition to interaction with other regulators, differential dimerization provides a plausible explanation for the observation that Pdr3p and Pdr1p can both positively and negatively control PDR promoters with different combinations of perfect and degenerate PDREs.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>12453227</pmid><doi>10.1046/j.1365-2958.2002.03262.x</doi><tpages>12</tpages></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Access via Wiley Online Library; Wiley Free Content; Free Full-Text Journals in Chemistry |
| subjects | ATP-Binding Cassette Transporters - genetics ATP-Binding Cassette Transporters - metabolism Dimerization DNA Footprinting DNA-Binding Proteins - chemistry DNA-Binding Proteins - metabolism Drug Resistance, Multiple, Fungal - genetics Gene Expression Regulation, Fungal Promoter Regions, Genetic - genetics Saccharomyces cerevisiae - drug effects Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae Proteins Trans-Activators - chemistry Trans-Activators - metabolism Transcription Factors - chemistry Transcription Factors - metabolism Transcription, Genetic Zinc Fingers |
| title | The yeast zinc finger regulators Pdr1p and Pdr3p control pleiotropic drug resistance (PDR) as homo‐ and heterodimers in vivo |
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