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dc.contributor.authorForés, Marta
dc.contributor.authorSimón-Carrasco, Lucía
dc.contributor.authorAjuria, Leiore
dc.contributor.authorSamper, Núria
dc.contributor.authorGonzález-Crespo, Sergio
dc.contributor.authorDrosten, Matthias 
dc.contributor.authorJiménez, Gerardo
dc.contributor.authorBarbacid, Mariano 
dc.date.accessioned2019-02-25T13:12:36Z
dc.date.available2019-02-25T13:12:36Z
dc.date.issued2017-03-09
dc.identifier.citationPLoS Genet. 2017;13(3):e1006622.es_ES
dc.identifier.issn1553-7404es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7232
dc.description.abstractHMG-box proteins, including Sox/SRY (Sox) and TCF/LEF1 (TCF) family members, bind DNA via their HMG-box. This binding, however, is relatively weak and both Sox and TCF factors employ distinct mechanisms for enhancing their affinity and specificity for DNA. Here we report that Capicua (CIC), an HMG-box transcriptional repressor involved in Ras/MAPK signaling and cancer progression, employs an additional distinct mode of DNA binding that enables selective recognition of its targets. We find that, contrary to previous assumptions, the HMG-box of CIC does not bind DNA alone but instead requires a distant motif (referred to as C1) present at the C-terminus of all CIC proteins. The HMG-box and C1 domains are both necessary for binding specific TGAATGAA-like sites, do not function via dimerization, and are active in the absence of cofactors, suggesting that they form a bipartite structure for sequence-specific binding to DNA. We demonstrate that this binding mechanism operates throughout Drosophila development and in human cells, ensuring specific regulation of multiple CIC targets. It thus appears that HMG-box proteins generally depend on auxiliary DNA binding mechanisms for regulating their appropriate genomic targets, but that each sub-family has evolved unique strategies for this purpose. Finally, the key role of C1 in DNA binding also explains the fact that this domain is a hotspot for inactivating mutations in oligodendroglioma and other tumors, while being preserved in oncogenic CIC-DUX4 fusion chimeras associated to Ewing-like sarcomas.es_ES
dc.description.sponsorshipWethankA.OlzaforDrosophilainjections,L.Campos,B.Lim,Z.Paroush,F.Port,S.Shvarts-man,A.VeraksaandJ. Vilardellfordiscussions;andJ.Jin,B.Edgar,C.MacKintosh,T.NakamuraandtheBloomingtonDrosophilaResearchCenterforreagents,plasmidsandstrains.es_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Sciencees_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshAmino Acid Motifs es_ES
dc.subject.meshAmino Acid Sequence es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshAnimals, Genetically Modified es_ES
dc.subject.meshBase Sequence es_ES
dc.subject.meshBinding Sites es_ES
dc.subject.meshDNA es_ES
dc.subject.meshDrosophila es_ES
dc.subject.meshDrosophila Proteins es_ES
dc.subject.meshEmbryo, Nonmammalian es_ES
dc.subject.meshHEK293 Cells es_ES
dc.subject.meshHMG-Box Domains es_ES
dc.subject.meshHMGB Proteins es_ES
dc.subject.meshHigh Mobility Group Proteins es_ES
dc.subject.meshHomeodomain Proteins es_ES
dc.subject.meshHumans es_ES
dc.subject.meshImmunohistochemistry es_ES
dc.subject.meshMicroscopy, Confocal es_ES
dc.subject.meshModels, Genetices_ES
dc.subject.meshNeoplasms es_ES
dc.subject.meshProtein Binding es_ES
dc.subject.meshRepressor Proteins es_ES
dc.subject.meshSequence Homology, Amino Acid es_ES
dc.subject.meshSequence Homology, Nucleic Acid es_ES
dc.subject.meshMutation es_ES
dc.titleA new mode of DNA binding distinguishes Capicua from other HMG-box factors and explains its mutation patterns in canceres_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID28278156es_ES
dc.format.volume13es_ES
dc.format.number3es_ES
dc.format.pagee1006622es_ES
dc.identifier.doi10.1371/journal.pgen.1006622es_ES
dc.contributor.funderMinisterio de Ciencia y Competitividad (España)es_ES
dc.contributor.funderEuropean Research Counciles_ES
dc.contributor.funderComunidad de Madrides_ES
dc.contributor.funderAXA Research Fundes_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1553-7404es_ES
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pgen.1006622.es_ES
dc.identifier.journalPLoS geneticses_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Oncología Experimentales_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BFU2011-23611es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BFU2014-52863Pes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/250297-RASAHEADes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2011-30173es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2014-59864Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/S2011/BDM-2470/ONCOCYCLEes_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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Atribución 4.0 Internacional
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