Identification of a candidate tumor-suppressor gene specifically activated during Ras-induced senescence

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dc.contributor.authorBarradas, M.en
dc.contributor.authorGonos, E. S.en
dc.contributor.authorZebedee, Z.en
dc.contributor.authorKolettas, E.en
dc.contributor.authorPetropoulou, C.en
dc.contributor.authorDelgado, M. D.en
dc.contributor.authorLeon, J.en
dc.contributor.authorHara, E.en
dc.contributor.authorSerrano, M.en
dc.date.accessioned2015-11-24T19:12:21Z
dc.date.available2015-11-24T19:12:21Z
dc.identifier.issn0014-4827-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/21061
dc.rightsDefault Licence-
dc.subjectAdenovirus E1A Proteins/metabolism/pharmacologyen
dc.subjectAdolescenten
dc.subjectAdulten
dc.subjectAgeden
dc.subjectAged, 80 and overen
dc.subjectCell Agingen
dc.subjectCell Divisionen
dc.subjectCell Lineen
dc.subjectChilden
dc.subjectDNA Damageen
dc.subject*DNA-Binding Proteinsen
dc.subjectFemaleen
dc.subjectFibroblasts/cytology/drug effectsen
dc.subject*Genes, Tumor Suppressoren
dc.subjectHumansen
dc.subjectHydrogen Peroxide/pharmacologyen
dc.subjectMembrane Proteinsen
dc.subjectMiddle Ageden
dc.subjectProto-Oncogene Protein c-ets-2en
dc.subjectProto-Oncogene Proteins/metabolismen
dc.subject*Repressor Proteinsen
dc.subjectTrans-Activators/metabolismen
dc.subject*Transcription Factorsen
dc.subject*Transcriptional Activationen
dc.subjectTumor Suppressor Proteins/*geneticsen
dc.subjectUp-Regulationen
dc.subjectras Proteins/*metabolism/pharmacologyen
dc.titleIdentification of a candidate tumor-suppressor gene specifically activated during Ras-induced senescenceen
heal.abstractNormal cells display protective responses against oncogenes. Notably, oncogenic Ras triggers an irreversible proliferation arrest that is reminiscent of replicative senescence and that is considered a relevant tumor-suppressor mechanism. Here, we have used microarrayed filters to identify genes specifically upregulated in Ras-senescent human fibroblasts. Among the initial set of genes selected from the microarrays, we found the cell-cycle inhibitor p21(Cip1/Waf1), thus validating the potency of the screening to identify markers and mediators of Ras-senescence. A group of six genes, formed by those more highly upregulated during Ras-senescence, was analyzed in further detail to evaluate their specificity. In particular, we examined their expression in cells overexpressing Ras but rendered resistant to Ras-senescence by the viral oncoprotein E1a; also, we have studied their expression during replicative senescence, organismal aging, H(2)O(2)-induced senescence, and DNA damage. In this manner, we have identified a novel gene, RIS1 (for Ras-induced senescence 1), which is not upregulated in association to any of the above-mentioned processes, but exclusively during Ras-senescence. Furthermore, RIS1 is also upregulated by the transcriptional factor Ets2, which is a known mediator of Ras-induced senescence. Interestingly, RIS1 is located at chromosomal position 3p21.3 and, more specifically, it is included in a short segment of just 1 Mb previously defined by other investigators for its tumor-suppressor activity. In summary, we report the identification of a novel gene, RIS1, as a highly specific marker of Ras-induced senescence and a candidate tumor-suppressor gene.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1006/excr.2001.5434-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/11822868-
heal.identifier.secondaryhttp://ac.els-cdn.com/S0014482701954345/1-s2.0-S0014482701954345-main.pdf?_tid=f1e4f1c724942279d52c19f7490a2c3e&acdnat=1332999248_c59a8ac9983c5733200a166f91441769-
heal.journalNameExp Cell Resen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2002-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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