title: The p53 isoform delta133p53ß regulates cancer cell apoptosis in a RhoB-dependent manner.
abstract: The TP53 gene plays essential roles in cancer. Conventionally, wild type (WT) p53 is thought to prevent cancer development and metastasis formation, while mutant p53 has transforming abilities. However, clinical studies failed to establish p53 mutation status as an unequivocal predictive or prognostic factor of cancer progression. The recent discovery of p53 isoforms that can differentially regulate cell cycle arrest and apoptosis suggests that their expression, rather than p53 mutations, could be a more clinically relevant biomarker in patients with cancer. In this study, we show that the p53 isoform delta133p53ß is involved in regulating the apoptotic response in colorectal cancer cell lines. We first demonstrate delta133p53ß association with the small GTPase RhoB, a well-described anti-apoptotic protein. We then show that, by inhibiting RhoB activity, delta133p53ß protects cells from camptothecin-induced apoptosis. Moreover, we found that high delta133p53 mRNA expression levels are correlated with higher risk of recurrence in a series of patients with locally advanced rectal cancer (n = 36). Our findings describe how a WT TP53 isoform can act as an oncogene and add a new layer to the already complex p53 signaling network.
authors.affiliation: CNRS, Centre de Recherche en Biologie cellulaire de Montpellier, Montpellier, France.|Université Montpellier, Montpellier, France.
authors.forename: Nikola
authors.initials: N
authors.lastname: Arsic
authors.affiliation: Translational Research Unit, Institut du Cancer de Montpellier, Montpellier, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Ho-Pun-Cheung
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lopez-Crapez
authors.affiliation: Department of Gastroenterology, Institut du Cancer de Montpellier, Montpellier, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Assenat
authors.affiliation: Biostatistics Department, Institut du Cancer de Montpellier, Montpellier, France.
authors.forename: Marta
authors.initials: M
authors.lastname: Jarlier
authors.affiliation: CNRS, Centre de Recherche en Biologie cellulaire de Montpellier, Montpellier, France.|Université Montpellier, Montpellier, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Anguille
authors.affiliation: CNRS, Centre de Recherche en Biologie cellulaire de Montpellier, Montpellier, France.|Université Montpellier, Montpellier, France.
authors.forename: Manon
authors.initials: M
authors.lastname: Colard
authors.affiliation: CNRS, Centre de Recherche en Biologie cellulaire de Montpellier, Montpellier, France.|Université Montpellier, Montpellier, France.
authors.forename: Mikaël
authors.initials: M
authors.lastname: Pezet
authors.affiliation: CNRS, Centre de Recherche en Biologie cellulaire de Montpellier, Montpellier, France.|Université Montpellier, Montpellier, France.|INSERM, Montpellier, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Roux
authors.affiliation: Université de la Réunion, Unité Mixte 134 Processus Infectieux en Milieu Insulaire Tropical, INSERM Unité 1187, CNRS Unité Mixte de Recherche 9192, IRD Unité Mixte de Recherche 249. Plateforme Technologique CYROI, Sainte Clotilde, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Gadea
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011379:Prognosis; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D020743:rhoB GTP-Binding Protein / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D020743:rhoB GTP-Binding Protein