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dc.contributor.authorJung, LAen
dc.contributor.authorGebhardt, Aen
dc.contributor.authorKoelmel, Wen
dc.contributor.authorAde, CPen
dc.contributor.authorWalz, Sen
dc.contributor.authorKuper, Jen
dc.contributor.authorvon Eyss, Ben
dc.contributor.authorLetschert, Sen
dc.contributor.authorRedel, Cen
dc.contributor.authord'Artista, Len
dc.contributor.authorBiankin, Aen
dc.contributor.authorZender, Len
dc.contributor.authorSauer, Men
dc.contributor.authorWolf, Een
dc.contributor.authorEvan, Gerarden
dc.contributor.authorKisker, Cen
dc.contributor.authorEilers, Men
dc.date.accessioned2019-08-05T14:43:21Z
dc.date.available2019-08-05T14:43:21Z
dc.date.issued2017-04-06en
dc.identifier.issn0950-9232
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/295282
dc.description.abstractMYC genes have both essential roles during normal development and exert oncogenic functions during tumorigenesis. Expression of a dominant-negative allele of MYC, termed OmoMYC, can induce rapid tumor regression in mouse models with little toxicity for normal tissues. How OmoMYC discriminates between physiological and oncogenic functions of MYC is unclear. We have solved the crystal structure of OmoMYC and show that it forms a stable homodimer and as such recognizes DNA in the same manner as the MYC/MAX heterodimer. OmoMYC attenuates both MYC-dependent activation and repression by competing with MYC/MAX for binding to chromatin, effectively lowering MYC/MAX occupancy at its cognate binding sites. OmoMYC causes the largest decreases in promoter occupancy and changes in expression on genes that are invaded by oncogenic MYC levels. A signature of OmoMYC-regulated genes defines subgroups with high MYC levels in multiple tumor entities and identifies novel targets for the eradication of MYC-driven tumors.
dc.languageengen
dc.language.isoenen
dc.publisherSpringer Nature [academic journals on nature.com]
dc.subjectBinding Sitesen
dc.subjectCells, Cultureden
dc.subjectDNAen
dc.subjectGene Expression Regulation, Neoplasticen
dc.subjectGenes, Dominanten
dc.subjectHumansen
dc.subjectModels, Molecularen
dc.subjectNeoplasmsen
dc.subjectPeptide Fragmentsen
dc.subjectPromoter Regions, Geneticen
dc.subjectProtein Multimerizationen
dc.subjectProto-Oncogene Proteins c-mycen
dc.subjectSequence Homologyen
dc.subjectTranscriptomeen
dc.subjectTumor Suppressor Proteinsen
dc.titleOmoMYC blunts promoter invasion by oncogenic MYC to inhibit gene expression characteristic of MYC-dependent tumors.en
dc.typeArticle
prism.endingPage1924
prism.issueIdentifier14en
prism.publicationDate2017en
prism.publicationNameOncogeneen
prism.startingPage1911
prism.volume36en
dc.identifier.doi10.17863/CAM.42334
dcterms.dateAccepted2016-08-15en
rioxxterms.versionofrecord10.1038/onc.2016.354en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-04-06en
dc.contributor.orcidEvan, Gerard [0000-0003-0412-1216]
dc.identifier.eissn1476-5594
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (19013)
pubs.funder-project-idCancer Research UK (22585)
cam.issuedOnline2016-10-17en


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