Cloning and Characterization of a Functional Peroxisome Proliferator Activator Receptor-γ-responsive Element in the Promoter of the CAP Gene
c-Cbl-associating protein (CAP) is a multifunctional signaling protein that interacts with c-Cbl, facilitating the tyrosine phosphorylation of c-Cbl in response to insulin. In 3T3-L1 adipocytes and diabetic rodents, CAPgene expression is stimulated by activators of peroxisome proliferator activator...
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| Veröffentlicht in: | The Journal of biological chemistry 2000-03, Vol.275 (13), p.9131-9135 |
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| creator | Baumann, Christian A. Chokshi, Neel Saltiel, Alan R. Ribon, Vered |
| description | c-Cbl-associating protein (CAP) is a multifunctional signaling protein that interacts with c-Cbl, facilitating the tyrosine phosphorylation of c-Cbl in response to insulin. In 3T3-L1 adipocytes and diabetic rodents, CAPgene expression is stimulated by activators of peroxisome proliferator activator receptor γ (PPARγ), such as thiazolidinediones (TZDs), resulting in increased insulin-stimulated c-Cbl phosphorylation. Sequence analysis of 2.5 kilobases of the 5′-flanking region of theCAP gene reveals a predicted peroxisome proliferator response element (PPRE) from −1085 to −1097. The isolated promoter was functional in 3T3 fibroblasts and adipocytes. Co-transfection of the CAP promoter with PPARγ and retinoic acid X receptor α caused fold stimulation of promoter activity. The TZD rosiglitazone produced an additional 2–3-fold stimulation of the promoter. Deletion of the predicted PPRE from the CAP promoter abolished its ability to respond to rosiglitazone. Gel shift analysis of the putative PPARγ site demonstrates direct binding of PPAR/retinoid X receptor heterodimers to the PPRE in the CAP gene. These data demonstrate that TZDs directly stimulate transcription of the CAP gene through activation of PPARγ. |
| doi_str_mv | 10.1074/jbc.275.13.9131 |
| format | Article |
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In 3T3-L1 adipocytes and diabetic rodents, CAPgene expression is stimulated by activators of peroxisome proliferator activator receptor γ (PPARγ), such as thiazolidinediones (TZDs), resulting in increased insulin-stimulated c-Cbl phosphorylation. Sequence analysis of 2.5 kilobases of the 5′-flanking region of theCAP gene reveals a predicted peroxisome proliferator response element (PPRE) from −1085 to −1097. The isolated promoter was functional in 3T3 fibroblasts and adipocytes. Co-transfection of the CAP promoter with PPARγ and retinoic acid X receptor α caused fold stimulation of promoter activity. The TZD rosiglitazone produced an additional 2–3-fold stimulation of the promoter. Deletion of the predicted PPRE from the CAP promoter abolished its ability to respond to rosiglitazone. Gel shift analysis of the putative PPARγ site demonstrates direct binding of PPAR/retinoid X receptor heterodimers to the PPRE in the CAP gene. These data demonstrate that TZDs directly stimulate transcription of the CAP gene through activation of PPARγ.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.275.13.9131</identifier><identifier>PMID: 10734046</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>3T3 Cells ; Animals ; Base Sequence ; c-Cbl-associating protein ; CAP gene ; Cloning, Molecular ; Cytoskeletal Proteins - genetics ; Dimerization ; DNA ; Humans ; Mice ; Molecular Sequence Data ; peroxisome proliferator-activated receptors ; Promoter Regions, Genetic ; Protein Binding ; Receptors, Cytoplasmic and Nuclear - genetics ; Receptors, Cytoplasmic and Nuclear - metabolism ; Receptors, Retinoic Acid - metabolism ; Retinoid X Receptors ; thiazolidinedione ; Transcription Factors - genetics ; Transcription Factors - metabolism</subject><ispartof>The Journal of biological chemistry, 2000-03, Vol.275 (13), p.9131-9135</ispartof><rights>2000 © 2000 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-7d93c3fa0b1de44eff1540f8089afdd027f4bc79814c6d5e90ede85bc14826953</citedby><cites>FETCH-LOGICAL-c415t-7d93c3fa0b1de44eff1540f8089afdd027f4bc79814c6d5e90ede85bc14826953</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10734046$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Baumann, Christian A.</creatorcontrib><creatorcontrib>Chokshi, Neel</creatorcontrib><creatorcontrib>Saltiel, Alan R.</creatorcontrib><creatorcontrib>Ribon, Vered</creatorcontrib><title>Cloning and Characterization of a Functional Peroxisome Proliferator Activator Receptor-γ-responsive Element in the Promoter of the CAP Gene</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>c-Cbl-associating protein (CAP) is a multifunctional signaling protein that interacts with c-Cbl, facilitating the tyrosine phosphorylation of c-Cbl in response to insulin. In 3T3-L1 adipocytes and diabetic rodents, CAPgene expression is stimulated by activators of peroxisome proliferator activator receptor γ (PPARγ), such as thiazolidinediones (TZDs), resulting in increased insulin-stimulated c-Cbl phosphorylation. Sequence analysis of 2.5 kilobases of the 5′-flanking region of theCAP gene reveals a predicted peroxisome proliferator response element (PPRE) from −1085 to −1097. The isolated promoter was functional in 3T3 fibroblasts and adipocytes. Co-transfection of the CAP promoter with PPARγ and retinoic acid X receptor α caused fold stimulation of promoter activity. The TZD rosiglitazone produced an additional 2–3-fold stimulation of the promoter. Deletion of the predicted PPRE from the CAP promoter abolished its ability to respond to rosiglitazone. Gel shift analysis of the putative PPARγ site demonstrates direct binding of PPAR/retinoid X receptor heterodimers to the PPRE in the CAP gene. These data demonstrate that TZDs directly stimulate transcription of the CAP gene through activation of PPARγ.</description><subject>3T3 Cells</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>c-Cbl-associating protein</subject><subject>CAP gene</subject><subject>Cloning, Molecular</subject><subject>Cytoskeletal Proteins - genetics</subject><subject>Dimerization</subject><subject>DNA</subject><subject>Humans</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>peroxisome proliferator-activated receptors</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Binding</subject><subject>Receptors, Cytoplasmic and Nuclear - genetics</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>Receptors, Retinoic Acid - metabolism</subject><subject>Retinoid X Receptors</subject><subject>thiazolidinedione</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcGKFDEQhoMo7rh69iY5eevZpJNMJ8eh2V2FBQdR8BbSScXN0p2MSc-w-g4-je_hM5ne2YMXsS5VBd__F9SP0GtK1pR0_OJusOu2E2vK1ooy-gStKJGsYYJ-eYpWhLS0Ua2QZ-hFKXekFlf0OTqrWsYJ36zQz35MMcSv2ESH-1uTjZ0hhx9mDini5LHBV4dol82MeAc53YeSJsC7nMbgIZs5ZbytwPFh-ggW9nVofv9qMpR9iiUcAV-OMEGccYh4vn0QT6neWQ4se7_d4WuI8BI982Ys8Oqxn6PPV5ef-nfNzYfr9_32prGcirnpnGKWeUMG6oBz8J4KTrwkUhnvHGk7zwfbKUm53TgBioADKQZLuWw3SrBz9Pbku8_p2wHKrKdQLIyjiZAORXeUMCYl-y9IO0FapUgFL06gzamUDF7vc5hM_q4p0UtUukala1SaMr1EVRVvHq0PwwTuL_6UTQXUCYD6iWOArIsNEC24kMHO2qXwT_M_b4Klqg</recordid><startdate>20000331</startdate><enddate>20000331</enddate><creator>Baumann, Christian A.</creator><creator>Chokshi, Neel</creator><creator>Saltiel, Alan R.</creator><creator>Ribon, Vered</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><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>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20000331</creationdate><title>Cloning and Characterization of a Functional Peroxisome Proliferator Activator Receptor-γ-responsive Element in the Promoter of the CAP Gene</title><author>Baumann, Christian A. ; 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In 3T3-L1 adipocytes and diabetic rodents, CAPgene expression is stimulated by activators of peroxisome proliferator activator receptor γ (PPARγ), such as thiazolidinediones (TZDs), resulting in increased insulin-stimulated c-Cbl phosphorylation. Sequence analysis of 2.5 kilobases of the 5′-flanking region of theCAP gene reveals a predicted peroxisome proliferator response element (PPRE) from −1085 to −1097. The isolated promoter was functional in 3T3 fibroblasts and adipocytes. Co-transfection of the CAP promoter with PPARγ and retinoic acid X receptor α caused fold stimulation of promoter activity. The TZD rosiglitazone produced an additional 2–3-fold stimulation of the promoter. Deletion of the predicted PPRE from the CAP promoter abolished its ability to respond to rosiglitazone. Gel shift analysis of the putative PPARγ site demonstrates direct binding of PPAR/retinoid X receptor heterodimers to the PPRE in the CAP gene. These data demonstrate that TZDs directly stimulate transcription of the CAP gene through activation of PPARγ.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>10734046</pmid><doi>10.1074/jbc.275.13.9131</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 3T3 Cells Animals Base Sequence c-Cbl-associating protein CAP gene Cloning, Molecular Cytoskeletal Proteins - genetics Dimerization DNA Humans Mice Molecular Sequence Data peroxisome proliferator-activated receptors Promoter Regions, Genetic Protein Binding Receptors, Cytoplasmic and Nuclear - genetics Receptors, Cytoplasmic and Nuclear - metabolism Receptors, Retinoic Acid - metabolism Retinoid X Receptors thiazolidinedione Transcription Factors - genetics Transcription Factors - metabolism |
| title | Cloning and Characterization of a Functional Peroxisome Proliferator Activator Receptor-γ-responsive Element in the Promoter of the CAP Gene |
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