Retinoic acid-dependent activation of the polycystic kidney disease-1 (PKD1) promoter
1 Department of Biochemistry and Molecular Biology, and the Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas; 2 Department of Chemistry/Physics, Northwest Missouri State University, Maryville, Missouri; and 3 Department of Biochemistry, Panjab University, Chandigarh, India...
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Veröffentlicht in: | American Journal of Physiology - Renal Physiology 2008-12, Vol.295 (6), p.F1845-F1854 |
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creator | Islam, M. Rafiq Puri, Sanjeev Rodova, Marianna Magenheimer, Brenda S Maser, Robin L Calvet, James P |
description | 1 Department of Biochemistry and Molecular Biology, and the Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas; 2 Department of Chemistry/Physics, Northwest Missouri State University, Maryville, Missouri; and 3 Department of Biochemistry, Panjab University, Chandigarh, India
Submitted 9 June 2008
; accepted in final form 9 October 2008
The retinoic acids all- trans retinoic acid (AT-RA) and 9- cis retinoic acid (9C-RA) and the retinoic acid receptors RAR and RXR significantly induce transcriptional activity from a 200-bp PKD1 proximal promoter in transfected mammalian cells. This PKD1 promoter region contains Ets, p53, and GC box motifs, but lacks a canonical RAR/RXR motif. Mutagenesis of the Ets sites did not affect RA induction. In contrast, GC box mutations completely blocked stimulation by AT-RA and by RXRβ or RARβ. Mithramycin A, which prevents Sp1 binding, significantly reduced basal promoter activity and suppressed upregulation by AT-RA and RXR. The 200-bp proximal promoter could not be induced by AT-RA in Drosophila SL2 cells, which lack Sp1, but could be activated in these cells transfected with exogenous Sp1. Small interfering RNA knockdown of Sp1 in mammalian cells completely blocked RXRβ upregulation of the promoter. These data indicate that induction of the PKD1 promoter by retinoic acid is mediated through Sp1 elements. RT-PCR showed that AT-RA treatment of HEK293T cells increased the levels of endogenous PKD1 RNA, and chromatin immunoprecipitation showed the presence of both RXR and Sp1 at the PKD1 proximal promoter. These results suggest that retinoids and their receptors may play a role in PKD1 gene regulation.
all- trans retinoic acid; 9- cis retinoic acid; RAR; RXR
Address for reprint requests and other correspondence: J. P. Calvet, Dept. of Biochemistry and Molecular Biology, Univ. of Kansas Medical Center, MS3030, Kansas City, KS 66160 (e-mail: jcalvet{at}kumc.edu ) |
doi_str_mv | 10.1152/ajprenal.90355.2008 |
format | Article |
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Submitted 9 June 2008
; accepted in final form 9 October 2008
The retinoic acids all- trans retinoic acid (AT-RA) and 9- cis retinoic acid (9C-RA) and the retinoic acid receptors RAR and RXR significantly induce transcriptional activity from a 200-bp PKD1 proximal promoter in transfected mammalian cells. This PKD1 promoter region contains Ets, p53, and GC box motifs, but lacks a canonical RAR/RXR motif. Mutagenesis of the Ets sites did not affect RA induction. In contrast, GC box mutations completely blocked stimulation by AT-RA and by RXRβ or RARβ. Mithramycin A, which prevents Sp1 binding, significantly reduced basal promoter activity and suppressed upregulation by AT-RA and RXR. The 200-bp proximal promoter could not be induced by AT-RA in Drosophila SL2 cells, which lack Sp1, but could be activated in these cells transfected with exogenous Sp1. Small interfering RNA knockdown of Sp1 in mammalian cells completely blocked RXRβ upregulation of the promoter. These data indicate that induction of the PKD1 promoter by retinoic acid is mediated through Sp1 elements. RT-PCR showed that AT-RA treatment of HEK293T cells increased the levels of endogenous PKD1 RNA, and chromatin immunoprecipitation showed the presence of both RXR and Sp1 at the PKD1 proximal promoter. These results suggest that retinoids and their receptors may play a role in PKD1 gene regulation.
all- trans retinoic acid; 9- cis retinoic acid; RAR; RXR
Address for reprint requests and other correspondence: J. P. Calvet, Dept. of Biochemistry and Molecular Biology, Univ. of Kansas Medical Center, MS3030, Kansas City, KS 66160 (e-mail: jcalvet{at}kumc.edu )</description><identifier>ISSN: 0363-6127</identifier><identifier>ISSN: 1931-857X</identifier><identifier>EISSN: 2161-1157</identifier><identifier>EISSN: 1522-1466</identifier><identifier>DOI: 10.1152/ajprenal.90355.2008</identifier><identifier>PMID: 18922886</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Animals ; Base Sequence ; Binding sites ; Cell Line ; Cells ; DNA Primers ; Genes ; Genes, Reporter ; Humans ; Iron-sulfur proteins ; Kidney - embryology ; Kidney diseases ; Luciferases - genetics ; Molecular Sequence Data ; Mutation ; Physiology ; Plasmids ; Promoter Regions, Genetic ; Receptors, Retinoic Acid - physiology ; Retinoid X Receptors - physiology ; Transcriptional Activation - drug effects ; Tretinoin - pharmacology ; Tretinoin - physiology ; TRPP Cation Channels - genetics</subject><ispartof>American Journal of Physiology - Renal Physiology, 2008-12, Vol.295 (6), p.F1845-F1854</ispartof><rights>Copyright American Physiological Society Dec 2008</rights><rights>Copyright © 2008, American Physiological Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c588t-d36d4372ca5b611be2f8567344c7d847894ca773aa57ed22f796fa86a0b1b9c83</citedby><cites>FETCH-LOGICAL-c588t-d36d4372ca5b611be2f8567344c7d847894ca773aa57ed22f796fa86a0b1b9c83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3039,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18922886$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Islam, M. Rafiq</creatorcontrib><creatorcontrib>Puri, Sanjeev</creatorcontrib><creatorcontrib>Rodova, Marianna</creatorcontrib><creatorcontrib>Magenheimer, Brenda S</creatorcontrib><creatorcontrib>Maser, Robin L</creatorcontrib><creatorcontrib>Calvet, James P</creatorcontrib><title>Retinoic acid-dependent activation of the polycystic kidney disease-1 (PKD1) promoter</title><title>American Journal of Physiology - Renal Physiology</title><addtitle>Am J Physiol Renal Physiol</addtitle><description>1 Department of Biochemistry and Molecular Biology, and the Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas; 2 Department of Chemistry/Physics, Northwest Missouri State University, Maryville, Missouri; and 3 Department of Biochemistry, Panjab University, Chandigarh, India
Submitted 9 June 2008
; accepted in final form 9 October 2008
The retinoic acids all- trans retinoic acid (AT-RA) and 9- cis retinoic acid (9C-RA) and the retinoic acid receptors RAR and RXR significantly induce transcriptional activity from a 200-bp PKD1 proximal promoter in transfected mammalian cells. This PKD1 promoter region contains Ets, p53, and GC box motifs, but lacks a canonical RAR/RXR motif. Mutagenesis of the Ets sites did not affect RA induction. In contrast, GC box mutations completely blocked stimulation by AT-RA and by RXRβ or RARβ. Mithramycin A, which prevents Sp1 binding, significantly reduced basal promoter activity and suppressed upregulation by AT-RA and RXR. The 200-bp proximal promoter could not be induced by AT-RA in Drosophila SL2 cells, which lack Sp1, but could be activated in these cells transfected with exogenous Sp1. Small interfering RNA knockdown of Sp1 in mammalian cells completely blocked RXRβ upregulation of the promoter. These data indicate that induction of the PKD1 promoter by retinoic acid is mediated through Sp1 elements. RT-PCR showed that AT-RA treatment of HEK293T cells increased the levels of endogenous PKD1 RNA, and chromatin immunoprecipitation showed the presence of both RXR and Sp1 at the PKD1 proximal promoter. These results suggest that retinoids and their receptors may play a role in PKD1 gene regulation.
all- trans retinoic acid; 9- cis retinoic acid; RAR; RXR
Address for reprint requests and other correspondence: J. P. Calvet, Dept. of Biochemistry and Molecular Biology, Univ. of Kansas Medical Center, MS3030, Kansas City, KS 66160 (e-mail: jcalvet{at}kumc.edu )</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Binding sites</subject><subject>Cell Line</subject><subject>Cells</subject><subject>DNA Primers</subject><subject>Genes</subject><subject>Genes, Reporter</subject><subject>Humans</subject><subject>Iron-sulfur proteins</subject><subject>Kidney - embryology</subject><subject>Kidney diseases</subject><subject>Luciferases - genetics</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Physiology</subject><subject>Plasmids</subject><subject>Promoter Regions, Genetic</subject><subject>Receptors, Retinoic Acid - physiology</subject><subject>Retinoid X Receptors - physiology</subject><subject>Transcriptional Activation - drug effects</subject><subject>Tretinoin - pharmacology</subject><subject>Tretinoin - physiology</subject><subject>TRPP Cation Channels - genetics</subject><issn>0363-6127</issn><issn>1931-857X</issn><issn>2161-1157</issn><issn>1522-1466</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU9v1DAQxS0EokvhEyChiBMcsvWfxHaEhIQKC4hKINSeLceebLxk49T2FvLt8bJLWw6cRqN5vzejeQg9J3hJSE3P9GYKMOph2WBW10uKsXyAFpRwUua5eIgWmHFWckLFCXoS4wZjSrnkj9EJkQ2lUvIFuvoOyY3emUIbZ0sLE4wWxpTb5G50cn4sfFekHorJD7OZY8raH86OMBfWRdARSlK8-vblPXldTMFvfYLwFD3q9BDh2bGeoqvVh8vzT-XF14-fz99dlKaWMpWWcVsxQY2uW05IC7STNResqoywshKyqYwWgmldC7CUdqLhnZZc45a0jZHsFL09-E67dgvW5MODHtQU3FaHWXnt1L-T0fVq7W8U5biSrMoGL48GwV_vICa18buQnxoVZZhQzOR-CzuITPAxBuhuFxCs9lGov1GoP1GofRSZenH_tjvm-PssODsIerfuf7oAaurn6Pzg1_OdI21qxdWKyKrOxJv_E6vdMFzCr3SL3iPVZDv2GxHQrkQ</recordid><startdate>20081201</startdate><enddate>20081201</enddate><creator>Islam, M. Rafiq</creator><creator>Puri, Sanjeev</creator><creator>Rodova, Marianna</creator><creator>Magenheimer, Brenda S</creator><creator>Maser, Robin L</creator><creator>Calvet, James P</creator><general>American Physiological Society</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>5PM</scope></search><sort><creationdate>20081201</creationdate><title>Retinoic acid-dependent activation of the polycystic kidney disease-1 (PKD1) promoter</title><author>Islam, M. Rafiq ; Puri, Sanjeev ; Rodova, Marianna ; Magenheimer, Brenda S ; Maser, Robin L ; Calvet, James P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c588t-d36d4372ca5b611be2f8567344c7d847894ca773aa57ed22f796fa86a0b1b9c83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Base Sequence</topic><topic>Binding sites</topic><topic>Cell Line</topic><topic>Cells</topic><topic>DNA Primers</topic><topic>Genes</topic><topic>Genes, Reporter</topic><topic>Humans</topic><topic>Iron-sulfur proteins</topic><topic>Kidney - embryology</topic><topic>Kidney diseases</topic><topic>Luciferases - genetics</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Physiology</topic><topic>Plasmids</topic><topic>Promoter Regions, Genetic</topic><topic>Receptors, Retinoic Acid - physiology</topic><topic>Retinoid X Receptors - physiology</topic><topic>Transcriptional Activation - drug effects</topic><topic>Tretinoin - pharmacology</topic><topic>Tretinoin - physiology</topic><topic>TRPP Cation Channels - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Islam, M. Rafiq</creatorcontrib><creatorcontrib>Puri, Sanjeev</creatorcontrib><creatorcontrib>Rodova, Marianna</creatorcontrib><creatorcontrib>Magenheimer, Brenda S</creatorcontrib><creatorcontrib>Maser, Robin L</creatorcontrib><creatorcontrib>Calvet, James P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American Journal of Physiology - Renal Physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Islam, M. Rafiq</au><au>Puri, Sanjeev</au><au>Rodova, Marianna</au><au>Magenheimer, Brenda S</au><au>Maser, Robin L</au><au>Calvet, James P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Retinoic acid-dependent activation of the polycystic kidney disease-1 (PKD1) promoter</atitle><jtitle>American Journal of Physiology - Renal Physiology</jtitle><addtitle>Am J Physiol Renal Physiol</addtitle><date>2008-12-01</date><risdate>2008</risdate><volume>295</volume><issue>6</issue><spage>F1845</spage><epage>F1854</epage><pages>F1845-F1854</pages><issn>0363-6127</issn><issn>1931-857X</issn><eissn>2161-1157</eissn><eissn>1522-1466</eissn><abstract>1 Department of Biochemistry and Molecular Biology, and the Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas; 2 Department of Chemistry/Physics, Northwest Missouri State University, Maryville, Missouri; and 3 Department of Biochemistry, Panjab University, Chandigarh, India
Submitted 9 June 2008
; accepted in final form 9 October 2008
The retinoic acids all- trans retinoic acid (AT-RA) and 9- cis retinoic acid (9C-RA) and the retinoic acid receptors RAR and RXR significantly induce transcriptional activity from a 200-bp PKD1 proximal promoter in transfected mammalian cells. This PKD1 promoter region contains Ets, p53, and GC box motifs, but lacks a canonical RAR/RXR motif. Mutagenesis of the Ets sites did not affect RA induction. In contrast, GC box mutations completely blocked stimulation by AT-RA and by RXRβ or RARβ. Mithramycin A, which prevents Sp1 binding, significantly reduced basal promoter activity and suppressed upregulation by AT-RA and RXR. The 200-bp proximal promoter could not be induced by AT-RA in Drosophila SL2 cells, which lack Sp1, but could be activated in these cells transfected with exogenous Sp1. Small interfering RNA knockdown of Sp1 in mammalian cells completely blocked RXRβ upregulation of the promoter. These data indicate that induction of the PKD1 promoter by retinoic acid is mediated through Sp1 elements. RT-PCR showed that AT-RA treatment of HEK293T cells increased the levels of endogenous PKD1 RNA, and chromatin immunoprecipitation showed the presence of both RXR and Sp1 at the PKD1 proximal promoter. These results suggest that retinoids and their receptors may play a role in PKD1 gene regulation.
all- trans retinoic acid; 9- cis retinoic acid; RAR; RXR
Address for reprint requests and other correspondence: J. P. Calvet, Dept. of Biochemistry and Molecular Biology, Univ. of Kansas Medical Center, MS3030, Kansas City, KS 66160 (e-mail: jcalvet{at}kumc.edu )</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>18922886</pmid><doi>10.1152/ajprenal.90355.2008</doi><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; American Physiological Society Paid; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
subjects | Animals Base Sequence Binding sites Cell Line Cells DNA Primers Genes Genes, Reporter Humans Iron-sulfur proteins Kidney - embryology Kidney diseases Luciferases - genetics Molecular Sequence Data Mutation Physiology Plasmids Promoter Regions, Genetic Receptors, Retinoic Acid - physiology Retinoid X Receptors - physiology Transcriptional Activation - drug effects Tretinoin - pharmacology Tretinoin - physiology TRPP Cation Channels - genetics |
title | Retinoic acid-dependent activation of the polycystic kidney disease-1 (PKD1) promoter |
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