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Conserved Double Translation Initiation Site for Δ160p53 Protein Hints at Isoform's Key Role in Mammalian Physiology

2022-12-13Journal article Open access
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dc.contributor.authorLópez-Iniesta, Maria José
dc.contributor.authorParker, Shrutee
dc.contributor.authorRamalho, Ana Catarina
dc.contributor.authorLacerda, Rafaela
dc.contributor.authorCosta, Inês
dc.contributor.authorZhao, Jingyuan
dc.contributor.authorRomão, Luísa
dc.contributor.authorCandeias, Marco
dc.date.accessioned2023-01-09T14:31:04Z
dc.date.available2023-01-09T14:31:04Z
dc.date.issued2022-12-13
dc.descriptionThis article belongs to the Special Issue p53 in Cancer and beyond—40 Years after Its Discoverypt_PT
dc.description.abstractp53 is the most commonly mutated gene in human cancers. Two fundamental reasons for this are its long protein isoforms protect from cancer, while its shorter C-terminal isoforms can support cancer and metastasis. Previously, we have shown that the Δ160p53 protein isoform enhances survival and the invasive character of cancer cells. Here, we identified a translation initiation site nine codons downstream of codon 160-the known initiation codon for the translation of Δ160p53-that is recognized by the translation machinery. When translation failed to initiate from AUG160 due to mutation, it initiated from AUG169 instead, producing similar levels of a similar protein, Δ169p53, which promoted cell survival as efficiently as Δ160p53 following DNA damage. Interestingly, almost all mammalian species with an orthologue to human AUG160 also possess one for AUG169, while none of the non-mammalian species lacking AUG160 have AUG169, even if that region of the p53 gene is well conserved. In view of our findings, we do not believe that Δ169p53 acts as a different p53 protein isoform; instead, we propose that the double translation initiation site strengthens the translation of these products with a critical role in cell homeostasis. Future studies will help verify if this is a more general mechanism for the expression of essential proteins in mammals.pt_PT
dc.description.sponsorshipThis research was funded by grants 18K07229 (KAKENHI) from Japan Society for the Promotion of Science (JSPS), PTDC/BIM-ONC/4890/2014 and PTDC/MED-ONC/32048/2017 from Fundação para a Ciência e a Tecnologia of Portugal (FCT) and grants/fellowships from Takeda Science Foundation (2017 Medical Research Fellowship (Oncology, Basic)), Astellas Research Foundation for Pathophysiology and Metabolism (project number 203180600044), AXA Research Fund, Ichiro Kanehara Foundation and Kyoto University (Ishizue, year 2021) attributed to M.M.C. This work was also partially supported by grant UID/MULTI/04046/2013 to BioISI from FCT/MCTES/PIDDAC and by funds from Instituto Nacional de Saúde Doutor Ricardo Jorge. M.J.L.I. and S.N.P. were partially supported by Otsuka Toshimi Scholarship Foundation. ACR is the recipient of a PhD scholarship from the Portuguese Foundation for Science and Technology (2020.06982.BD)pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInt J Mol Sci. 2022 Dec 13;23(24):15844. doi: 10.3390/ijms232415844.pt_PT
dc.identifier.doi10.3390/ijms232415844pt_PT
dc.identifier.issn1661-6596
dc.identifier.urihttp://hdl.handle.net/10400.18/8407
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationStudying and targeting the non-canonical translation of p53 isoforms during stress and carcinogenesis
dc.relationStudying and targeting the non-coding functions of p53 mRNA in carcinogenesis
dc.relationBiosystems & Integrative Sciences Institute
dc.relationUnraveling the oncogenic functions and regulation of the most conserved p53 isoform, 160p53: a study in cancer cells and transgenic mice
dc.relation.publisherversionhttps://www.mdpi.com/resolver?pii=ijms232415844pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectCancerpt_PT
dc.subjectp53pt_PT
dc.subjectp53 isoformpt_PT
dc.subjectp53 mRNApt_PT
dc.subjectTranslationpt_PT
dc.subjectΔ160p53pt_PT
dc.subjectExpressão Génicapt_PT
dc.subjectGenómica Funcional e Estruturalpt_PT
dc.titleConserved Double Translation Initiation Site for Δ160p53 Protein Hints at Isoform's Key Role in Mammalian Physiologypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleStudying and targeting the non-canonical translation of p53 isoforms during stress and carcinogenesis
oaire.awardTitleStudying and targeting the non-coding functions of p53 mRNA in carcinogenesis
oaire.awardTitleBiosystems & Integrative Sciences Institute
oaire.awardTitleUnraveling the oncogenic functions and regulation of the most conserved p53 isoform, 160p53: a study in cancer cells and transgenic mice
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIM-ONC%2F4890%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FMED-ONC%2F32048%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F04046%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/2020.06982.BD/PT
oaire.citation.issue24pt_PT
oaire.citation.startPage15844pt_PT
oaire.citation.titleInternational Journal of Molecular Sciencespt_PT
oaire.citation.volume23pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamOE
person.familyNameRomão
person.givenNameLuísa
person.identifierhttps://scholar.google.pt/citations?hl=pt-PT&user=CAHjIsoAAAAJ&cstart=60&pagesize=20
person.identifier.ciencia-idEB19-DF07-EB37
person.identifier.orcid0000-0002-5061-5287
person.identifier.scopus-author-idhttp://www.scopus.com/authid/detail.url?authorId=6602834878
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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