The coding sequence mediates induction of 5-lipoxygenase expression by Smads3/4
5-Lipoxygenase ( 5-LO) expression is strongly induced by transforming growth factor-β (TGFβ) and 1α,25-dihydroxyvitamin D 3 in Mono Mac 6 cells. Since Smads have been described as downstream effectors of TGFβ, we have investigated the role of the TGFβ/Smad signalling system in the regulation of 5-LO...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2006-10, Vol.348 (4), p.1403-1410 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Seuter, Sabine Sorg, Bernd L. Steinhilber, Dieter |
| description | 5-Lipoxygenase (
5-LO) expression is strongly induced by transforming growth factor-β (TGFβ) and 1α,25-dihydroxyvitamin D
3 in Mono Mac 6 cells. Since Smads have been described as downstream effectors of TGFβ, we have investigated the role of the TGFβ/Smad signalling system in the regulation of
5-LO gene expression. The rapid induction of 5-LO mRNA, determined with real-time quantitative RT-PCR, suggests that 5-LO is a primary TGFβ target gene. In reporter gene assays with plasmids containing the
5-LO promoter plus different parts of the gene, Smads3/4 mediate a prominent upregulation of reporter activity that strongly depends on the coding sequence and to a lesser extent on the 3′-UTR and introns J-M. Deletion studies revealed the most profound decrease of inducibility by Smads3/4 when exons 10–14 are deleted. Sequence analysis and deletion studies indicate the existence of up to four Smad binding elements and at least one TGFβ responsive element far downstream of the transcriptional start site. |
| doi_str_mv | 10.1016/j.bbrc.2006.08.011 |
| format | Article |
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5-LO) expression is strongly induced by transforming growth factor-β (TGFβ) and 1α,25-dihydroxyvitamin D
3 in Mono Mac 6 cells. Since Smads have been described as downstream effectors of TGFβ, we have investigated the role of the TGFβ/Smad signalling system in the regulation of
5-LO gene expression. The rapid induction of 5-LO mRNA, determined with real-time quantitative RT-PCR, suggests that 5-LO is a primary TGFβ target gene. In reporter gene assays with plasmids containing the
5-LO promoter plus different parts of the gene, Smads3/4 mediate a prominent upregulation of reporter activity that strongly depends on the coding sequence and to a lesser extent on the 3′-UTR and introns J-M. Deletion studies revealed the most profound decrease of inducibility by Smads3/4 when exons 10–14 are deleted. Sequence analysis and deletion studies indicate the existence of up to four Smad binding elements and at least one TGFβ responsive element far downstream of the transcriptional start site.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2006.08.011</identifier><identifier>PMID: 16919603</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>5-Lipoxygenase ; Arachidonate 5-Lipoxygenase - biosynthesis ; Arachidonate 5-Lipoxygenase - genetics ; Calcitriol - pharmacology ; Coding sequence ; Exons ; Gene expression ; Gene Expression Regulation, Enzymologic ; Genes, Reporter ; HeLa Cells ; Humans ; Receptors, Calcitriol - metabolism ; Reporter gene assay ; Response element ; Response Elements ; Retinoid X Receptors - metabolism ; Smad3 Protein - metabolism ; Smad3/4 ; Smad4 Protein - metabolism ; Transcriptional Activation ; Transforming Growth Factor beta - pharmacology ; Transforming growth factor-β</subject><ispartof>Biochemical and biophysical research communications, 2006-10, Vol.348 (4), p.1403-1410</ispartof><rights>2006 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c385t-7201b2e3f0f10d0255f55b8dd6175982a6c9696b5c3f8a1b58c9dd2e49e035b23</citedby><cites>FETCH-LOGICAL-c385t-7201b2e3f0f10d0255f55b8dd6175982a6c9696b5c3f8a1b58c9dd2e49e035b23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X06017852$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16919603$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Seuter, Sabine</creatorcontrib><creatorcontrib>Sorg, Bernd L.</creatorcontrib><creatorcontrib>Steinhilber, Dieter</creatorcontrib><title>The coding sequence mediates induction of 5-lipoxygenase expression by Smads3/4</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>5-Lipoxygenase (
5-LO) expression is strongly induced by transforming growth factor-β (TGFβ) and 1α,25-dihydroxyvitamin D
3 in Mono Mac 6 cells. Since Smads have been described as downstream effectors of TGFβ, we have investigated the role of the TGFβ/Smad signalling system in the regulation of
5-LO gene expression. The rapid induction of 5-LO mRNA, determined with real-time quantitative RT-PCR, suggests that 5-LO is a primary TGFβ target gene. In reporter gene assays with plasmids containing the
5-LO promoter plus different parts of the gene, Smads3/4 mediate a prominent upregulation of reporter activity that strongly depends on the coding sequence and to a lesser extent on the 3′-UTR and introns J-M. Deletion studies revealed the most profound decrease of inducibility by Smads3/4 when exons 10–14 are deleted. Sequence analysis and deletion studies indicate the existence of up to four Smad binding elements and at least one TGFβ responsive element far downstream of the transcriptional start site.</description><subject>5-Lipoxygenase</subject><subject>Arachidonate 5-Lipoxygenase - biosynthesis</subject><subject>Arachidonate 5-Lipoxygenase - genetics</subject><subject>Calcitriol - pharmacology</subject><subject>Coding sequence</subject><subject>Exons</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Genes, Reporter</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Receptors, Calcitriol - metabolism</subject><subject>Reporter gene assay</subject><subject>Response element</subject><subject>Response Elements</subject><subject>Retinoid X Receptors - metabolism</subject><subject>Smad3 Protein - metabolism</subject><subject>Smad3/4</subject><subject>Smad4 Protein - metabolism</subject><subject>Transcriptional Activation</subject><subject>Transforming Growth Factor beta - pharmacology</subject><subject>Transforming growth factor-β</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEFLJDEQhcOirKO7f8CD9Mlbt1VJJ9MBLyK6KwgedGFvoZNUa4aZ7jHpEeffm2YGvOmpDu97j-Jj7BShQkB1saisja7iAKqCpgLEH2yGoKHkCPUBm0FOSq7x_xE7TmkBmaiV_smOUGnUCsSMPTy9UOEGH_rnItHrhnpHxYp8aEdKRej9xo1h6IuhK2S5DOvhfftMfZuooPd1pJSm0G6Lx1Xrk7iof7HDrl0m-r2_J-zf7c3T9d_y_uHP3fXVfelEI8dyzgEtJ9FBh-CBS9lJaRvvFc6lbnirnFZaWelE17RoZeO095xqTSCk5eKEne9213HIX6fRrEJytFy2PQ2bZFQz18jr-lsQtahBC5lBvgNdHFKK1Jl1DKs2bg2CmXybhZl8m8m3gcZkm7l0tl_f2Gzts7IXnIHLHUBZxlugaJILk2QfIrnR-CF8tf8BghSQUA</recordid><startdate>20061006</startdate><enddate>20061006</enddate><creator>Seuter, Sabine</creator><creator>Sorg, Bernd L.</creator><creator>Steinhilber, Dieter</creator><general>Elsevier Inc</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>7TM</scope><scope>7X8</scope></search><sort><creationdate>20061006</creationdate><title>The coding sequence mediates induction of 5-lipoxygenase expression by Smads3/4</title><author>Seuter, Sabine ; Sorg, Bernd L. ; Steinhilber, Dieter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c385t-7201b2e3f0f10d0255f55b8dd6175982a6c9696b5c3f8a1b58c9dd2e49e035b23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>5-Lipoxygenase</topic><topic>Arachidonate 5-Lipoxygenase - biosynthesis</topic><topic>Arachidonate 5-Lipoxygenase - genetics</topic><topic>Calcitriol - pharmacology</topic><topic>Coding sequence</topic><topic>Exons</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Genes, Reporter</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Receptors, Calcitriol - metabolism</topic><topic>Reporter gene assay</topic><topic>Response element</topic><topic>Response Elements</topic><topic>Retinoid X Receptors - metabolism</topic><topic>Smad3 Protein - metabolism</topic><topic>Smad3/4</topic><topic>Smad4 Protein - metabolism</topic><topic>Transcriptional Activation</topic><topic>Transforming Growth Factor beta - pharmacology</topic><topic>Transforming growth factor-β</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Seuter, Sabine</creatorcontrib><creatorcontrib>Sorg, Bernd L.</creatorcontrib><creatorcontrib>Steinhilber, Dieter</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Seuter, Sabine</au><au>Sorg, Bernd L.</au><au>Steinhilber, Dieter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The coding sequence mediates induction of 5-lipoxygenase expression by Smads3/4</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2006-10-06</date><risdate>2006</risdate><volume>348</volume><issue>4</issue><spage>1403</spage><epage>1410</epage><pages>1403-1410</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>5-Lipoxygenase (
5-LO) expression is strongly induced by transforming growth factor-β (TGFβ) and 1α,25-dihydroxyvitamin D
3 in Mono Mac 6 cells. Since Smads have been described as downstream effectors of TGFβ, we have investigated the role of the TGFβ/Smad signalling system in the regulation of
5-LO gene expression. The rapid induction of 5-LO mRNA, determined with real-time quantitative RT-PCR, suggests that 5-LO is a primary TGFβ target gene. In reporter gene assays with plasmids containing the
5-LO promoter plus different parts of the gene, Smads3/4 mediate a prominent upregulation of reporter activity that strongly depends on the coding sequence and to a lesser extent on the 3′-UTR and introns J-M. Deletion studies revealed the most profound decrease of inducibility by Smads3/4 when exons 10–14 are deleted. Sequence analysis and deletion studies indicate the existence of up to four Smad binding elements and at least one TGFβ responsive element far downstream of the transcriptional start site.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>16919603</pmid><doi>10.1016/j.bbrc.2006.08.011</doi><tpages>8</tpages></addata></record> |
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| subjects | 5-Lipoxygenase Arachidonate 5-Lipoxygenase - biosynthesis Arachidonate 5-Lipoxygenase - genetics Calcitriol - pharmacology Coding sequence Exons Gene expression Gene Expression Regulation, Enzymologic Genes, Reporter HeLa Cells Humans Receptors, Calcitriol - metabolism Reporter gene assay Response element Response Elements Retinoid X Receptors - metabolism Smad3 Protein - metabolism Smad3/4 Smad4 Protein - metabolism Transcriptional Activation Transforming Growth Factor beta - pharmacology Transforming growth factor-β |
| title | The coding sequence mediates induction of 5-lipoxygenase expression by Smads3/4 |
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