Publicação
Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene
| dc.contributor.author | Kirfel, J | |
| dc.contributor.author | Kelter, M | |
| dc.contributor.author | Cancela, LM | |
| dc.contributor.author | Price, PA | |
| dc.contributor.author | Schule, R | |
| dc.date.accessioned | 2018-12-07T14:53:47Z | |
| dc.date.available | 2018-12-07T14:53:47Z | |
| dc.date.issued | 1997 | |
| dc.description.abstract | The vitamin K-dependent matrix Gla protein (MGP) is synthesized in a wide variety of tissues such as lung, heart, kidney, cartilage, and bone, Expression of the MGP gene is regulated by various growth factors, steroid hormones, and the vitamin A metabolite retinoic acid (RA). In this report, we present evidence that RA down-regulates MGP gene expression in different rat and human cell lines via endogenous retinoid receptors [RA receptor (RAR) and retinoid X receptor (RXR)], Repression of the human MGP (hMGP) gene is specifically mediated by ligand-activated RAR and RXR, Deletion analysis led to the identification of a novel negative response element (NRE) within the hMGP promoter, DNA binding studies performed with bacterially expressed RAR/RXR reveal the formation of a specific heterodimer/ NRE complex, Furthermore, electrophoretic mobility-shift assays performed with proteins from RA-treated cells show that endogenous RAR/RXR binds to the NRE. We demonstrate that the NRE contains a CCAAT box and that both RAR/RXR and CCAAT-binding proteins such as c/EBP beta recognize this common regulatory sequence in the hMGP promoter, Our results indicate that RA-mediated repression of the hMGP gene is due to binding of liganded RAR/RXR to a novel negative RA response element. | |
| dc.description.sponsorship | NIAMS NIH HHS [AR25921] | |
| dc.description.version | info:eu-repo/semantics/publishedVersion | |
| dc.identifier.doi | 10.1073/pnas.94.6.2227 | |
| dc.identifier.issn | 0027-8424 | |
| dc.identifier.uri | http://hdl.handle.net/10400.1/11683 | |
| dc.language.iso | eng | |
| dc.peerreviewed | yes | |
| dc.publisher | Natl Acad Sciences | |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
| dc.subject | Thyroid-hormone | |
| dc.subject | Messenger-Rna | |
| dc.subject | Co-repressor | |
| dc.subject | Cells | |
| dc.subject | Receptors | |
| dc.subject | Rat | |
| dc.subject | Transcription | |
| dc.subject | Expression | |
| dc.subject | Cartilage | |
| dc.title | Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene | |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 2232 | |
| oaire.citation.issue | 6 | |
| oaire.citation.startPage | 2227 | |
| oaire.citation.title | Proceedings of the National Academy of Sciences | |
| oaire.citation.volume | 94 | |
| person.familyName | Cancela | |
| person.givenName | M. Leonor | |
| person.identifier.orcid | 0000-0003-3114-6662 | |
| rcaap.rights | openAccess | |
| rcaap.type | article | |
| relation.isAuthorOfPublication | b9bbfe32-3dfe-4131-ad14-a4394008447f | |
| relation.isAuthorOfPublication.latestForDiscovery | b9bbfe32-3dfe-4131-ad14-a4394008447f |
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