title: A novel cytoprotective function for the DNA repair protein Ku in regulating p53 mRNA translation and function.
abstract: Ku heterodimer is a DNA binding protein with a prominent role in DNA repair. Here, we investigate whether and how Ku impacts the DNA damage response by acting as a post-transcriptional regulator of gene expression. We show that Ku represses p53 protein synthesis and p53-mediated apoptosis by binding to a bulged stem-loop structure within the p53 5' UTR However, Ku-mediated translational repression of the p53 mRNA is relieved after genotoxic stress. The underlying mechanism involves Ku acetylation which disrupts Ku-p53 mRNA interactions. These results suggest that Ku-mediated repression of p53 mRNA translation constitutes a novel mechanism linking DNA repair and mRNA translation.
authors.affiliation: Cancer Research Center of Toulouse (CRCT), Inserm UMR 1037 Université Toulouse III-Paul Sabatier, Toulouse, France.
authors.forename: Assala
authors.initials: A
authors.lastname: Lamaa
authors.affiliation: Cancer Research Center of Toulouse (CRCT), Inserm UMR 1037 Université Toulouse III-Paul Sabatier, Toulouse, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Le Bras
authors.affiliation: Cancer Research Center of Toulouse (CRCT), Inserm UMR 1037 Université Toulouse III-Paul Sabatier, Toulouse, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Skuli
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS UPS, France Equipe labellisée Ligue Nationale Contre le Cancer.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Britton
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS UPS, France Equipe labellisée Ligue Nationale Contre le Cancer.
authors.forename: Philippe
authors.initials: P
authors.lastname: Frit
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS UPS, France Equipe labellisée Ligue Nationale Contre le Cancer.
authors.forename: Patrick
authors.initials: P
authors.lastname: Calsou
authors.affiliation: Cancer Research Center of Toulouse (CRCT), Inserm UMR 1037 Université Toulouse III-Paul Sabatier, Toulouse, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Prats
authors.affiliation: Cancer Research Center of Toulouse (CRCT), Inserm UMR 1037 Université Toulouse III-Paul Sabatier, Toulouse, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Cammas
authors.affiliation: Cancer Research Center of Toulouse (CRCT), Inserm UMR 1037 Université Toulouse III-Paul Sabatier, Toulouse, France stefania.millevoi@inserm.fr.
authors.forename: Stefania
authors.initials: S
authors.lastname: Millevoi
mesh_terms: D020121:5' Untranslated Regions; D000107:Acetylation; D017209:Apoptosis; D004249:DNA Damage / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D000072200:Ku Autoantigen / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000072200:Ku Autoantigen
keywords: DNA damage; Ku; mRNA translation; p53