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Regulation of IRES-mediated translation in p53

2020-11-20Conference object Restricted access
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dc.contributor.authorFonseca Costa, Inês
dc.contributor.authorLacerda, Rafaela
dc.contributor.authorLópez-Iniesta, M.
dc.contributor.authorRomão, Luísa
dc.contributor.authorCandeias, Marco M.
dc.date.accessioned2021-03-13T16:04:09Z
dc.date.embargo2025-12-31
dc.date.issued2020-11-20
dc.description.abstractThe tumor microenvironment is characterized by several stresses impairing canonical translation. However, specific mRNAs harbouring internal ribosome entry sites (IRES), such as several tumour suppressors and oncogenes, can overcome this impairment. The tumor suppressor TP53 gene, an important transcription factor that ensures cellular homeostasis, is frequently mutated in human cancers. Over the years, several p53 isoforms have been identified, which in some cases result from alternative initiation of translation regulated by an IRES. Recently, we have associated mutant p53 “gain-of-function” cancer phenotype, such as enhanced cell survival, invasion, proliferation, and adhesion, with the expression of higher levels of shorter p53 isoforms, such as Δ160p53 isoform.1 Here, we used a bicistronic system containing two reporter luciferases (renilla luciferase and firefly luciferase) to assess IRES-mediated translation. Several p53 mRNA elements were tested in this system and, interestingly, we have found an inhibitory element of IRES-mediated translation. Overall, IRES-regulated translation in malignant cells is used to translate specific proteins that promote cancer progression. Thus, inhibiting translation of oncogenes via IRES could prevent the formation of tumor cells and their adaptation to unfavourable conditions in the tumor microenvironment. 1. Candeias, M. M., Hagiwara, M. & Matsuda, M. Cancer‐specific mutations in p53 induce the translation of Δ160p53 promoting tumorigenesis. EMBO Rep. 17, 1542–1551 (2016).pt_PT
dc.description.sponsorshipThe project is funded by FCT grant PTDC/MED-ONC/32048/2017pt_PT
dc.description.versionN/Apt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/7455
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationStudying and targeting the non-coding functions of p53 mRNA in carcinogenesis
dc.subjectTumorpt_PT
dc.subjectCancerpt_PT
dc.subjectIRES-mediated Translationpt_PT
dc.subjectp53pt_PT
dc.subjectGenómica Funcional e Estruturalpt_PT
dc.titleRegulation of IRES-mediated translation in p53pt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.awardTitleStudying and targeting the non-coding functions of p53 mRNA in carcinogenesis
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FMED-ONC%2F32048%2F2017/PT
oaire.citation.conferencePlaceLisboa, Portugal (online)pt_PT
oaire.citation.title24ª Reunião Científica da Sociedade Portuguesa de Genética Humana, 20 novembro 2020pt_PT
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsembargoedAccesspt_PT
rcaap.typeconferenceObjectpt_PT
relation.isProjectOfPublication6a8083d6-0c9b-4c73-a81b-fd723a022f17
relation.isProjectOfPublication.latestForDiscovery6a8083d6-0c9b-4c73-a81b-fd723a022f17

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