Tert Promoter Mutations In Melanoma Render Tert Expression Dependent On Mapk Pathway Activation

dc.creatorVallarelli
dc.creatorAndrelou F.; Rachakonda
dc.creatorP. Sivaramakrishna; Andre
dc.creatorJocelyne; Heidenreich
dc.creatorBarbara; Riffaud
dc.creatorLaurence; Bensussan
dc.creatorArmand; Kumar
dc.creatorRajiv; Dumaz
dc.creatorNicolas
dc.date2016
dc.dateagos
dc.date2017-11-13T13:43:29Z
dc.date2017-11-13T13:43:29Z
dc.date.accessioned2018-03-29T05:58:12Z
dc.date.available2018-03-29T05:58:12Z
dc.identifierOncotarget. Impact Journals Llc, v. 7, p. 53127 - 53136, 2016.
dc.identifier1949-2553
dc.identifierWOS:000385433000039
dc.identifier10.18632/oncotarget.10634
dc.identifierhttp://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=10634&pubmed-linkout=1
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/328565
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1365590
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionThe mechanism of telomerase re-activation in cancer had remained elusive until the discovery of frequent mutations in the promoter of the TERT gene that encodes the catalytic reverse transcriptase subunit of telomerase. We investigated the regulation of TERT expression in melanoma cell lines and our results show that promoter mutations render TERT expression dependent on MAPK activation due to oncogenic BRAF or NRAS mutations. Mutations in the TERT promoter create binding sites for ETS transcription factors. ETS1, expressed in melanoma cell lines, undergoes activating phosphorylation by ERK at Thr38 residue as a consequence of constitutively activated MAPK pathway. We demonstrate that ETS1 binds on the mutated TERT promoter leading to the re-expression of the gene. The inhibition of ETS1 resulted in reduced TERT expression. We provide evidence that the TERT promoter mutations provide a direct link between TERT expression and MAPK pathway activation due to BRAF or NRAS mutations via the transcription factor ETS1.
dc.description7
dc.description33
dc.description53127
dc.description53136
dc.descriptionCAPES - Brazilian Federal Agency for Support and Evaluation of Graduate Education within the Ministry of Education of Brazil
dc.descriptionLigue Contre le Cancer Comite de Paris
dc.descriptionGEFLUC Paris-Ile-de-France
dc.descriptionFondation ARC pour la Recherche sur le Cancer
dc.descriptionINSERM
dc.descriptionUniversite Paris Diderot
dc.descriptionTRANSCAN through German Ministry of Education and Science [01KT1511]
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.languageEnglish
dc.publisherImpact Journals Llc
dc.publisherAlbany
dc.relationOncotarget
dc.rightsaberto
dc.sourceWOS
dc.subjectMelanoma
dc.subjectTelomerase
dc.subjectEts1
dc.subjectMapk Pathway
dc.subjectBraf
dc.titleTert Promoter Mutations In Melanoma Render Tert Expression Dependent On Mapk Pathway Activation
dc.typeArtículos de revistas


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