Publication
Cancer-specific mutations in p53 induce the translation of Δ160p53 promoting tumorigenesis
| dc.contributor.author | Candeias, Marco | |
| dc.contributor.author | Hagiwara, Masatoshi | |
| dc.contributor.author | Matsuda, Michiyuki | |
| dc.date.accessioned | 2017-03-02T13:17:06Z | |
| dc.date.available | 2017-03-02T13:17:06Z | |
| dc.date.issued | 2016-11 | |
| dc.description.abstract | Wild-type p53 functions as a tumour suppressor while mutant p53 possesses oncogenic potential. Until now it remains unclear how a single mutation can transform p53 into a functionally distinct gene harbouring a new set of original cellular roles. Here we show that the most common p53 cancer mutants express a larger number and higher levels of shorter p53 protein isoforms that are translated from the mutated full-length p53 mRNA. Cells expressing mutant p53 exhibit "gain-of-function" cancer phenotypes, such as enhanced cell survival, proliferation, invasion and adhesion, altered mammary tissue architecture and invasive cell structures. Interestingly, Δ160p53-overexpressing cells behave in a similar manner. In contrast, an exogenous or endogenous mutant p53 that fails to express Δ160p53 due to specific mutations or antisense knock-down loses pro-oncogenic potential. Our data support a model in which "gain-of-function" phenotypes induced by p53 mutations depend on the shorter p53 isoforms. As a conserved wild-type isoform, Δ160p53 has evolved during millions of years. We thus provide a rational explanation for the origin of the tumour-promoting functions of p53 mutations. | pt_PT |
| dc.description.sponsorship | This research was supported mainly by Grant-in-Aid for Scientific Research on the Innovative Area of “Resonance Biology” (No. 15H0594) of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) attributed to M.M.; but also by JSPS KAKENHI Grant-in-Aid for Scientific Research (S) Grant Number 15H05721 attributed to M.H. and Grant PTDC/BIM-ONC/4890/2014 from the Fundação para a Ciência e a Tecnologia (FCT) attributed to M.M.C. M.M.C. was supported by grants from the Japan Society for the Promotion of Science (JSPS Postdoctoral Fellowship), AXA Research Fund and the Ichiro Kanehara Foundation. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | EMBO Rep. 2016 Nov;17(11):1542-1551. doi:10.15252/embr.201541956. Epub 2016 Oct 4 | pt_PT |
| dc.identifier.doi | 10.15252/embr.201541956 | pt_PT |
| dc.identifier.issn | 1469-221X | |
| dc.identifier.uri | http://hdl.handle.net/10400.18/4395 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | EMBO Press | pt_PT |
| dc.relation.publisherversion | http://embor.embopress.org/content/17/11/1542.long | pt_PT |
| dc.subject | Cancer | pt_PT |
| dc.subject | GOFs | pt_PT |
| dc.subject | Mutant p53 | pt_PT |
| dc.subject | p53 mRNA | pt_PT |
| dc.subject | p53 Isoforms | pt_PT |
| dc.subject | Δ160p53 | pt_PT |
| dc.subject | Cancro | pt_PT |
| dc.subject | Expressão Génica | pt_PT |
| dc.subject | Genómica Funcional e Estrutural | pt_PT |
| dc.title | Cancer-specific mutations in p53 induce the translation of Δ160p53 promoting tumorigenesis | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 1551 | pt_PT |
| oaire.citation.startPage | 1542 | pt_PT |
| oaire.citation.title | EMBO Reports | pt_PT |
| oaire.citation.volume | 17(11) | pt_PT |
| rcaap.rights | embargoedAccess | pt_PT |
| rcaap.type | article | pt_PT |