Lamaa Assala, Le Bras Morgane, Skuli Nicolas, Britton Sébastien, Frit Philippe, Calsou Patrick, Prats Hervé, Cammas Anne, Millevoi Stefania
Cancer Research Center of Toulouse (CRCT), Inserm UMR 1037 Université Toulouse III-Paul Sabatier, Toulouse, France.
Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS UPS, France Equipe labellisée Ligue Nationale Contre le Cancer.
EMBO Rep. 2016 Apr;17(4):508-18. doi: 10.15252/embr.201541181. Epub 2016 Mar 10.
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.
Ku异二聚体是一种在DNA修复中起重要作用的DNA结合蛋白。在此，我们研究Ku是否以及如何通过作为基因表达的转录后调节因子来影响DNA损伤反应。我们发现Ku通过与p53 5'非翻译区内的一个凸起茎环结构结合来抑制p53蛋白合成和p53介导的细胞凋亡。然而，在基因毒性应激后，Ku介导的p53 mRNA翻译抑制作用会解除。潜在机制涉及Ku乙酰化，它会破坏Ku与p53 mRNA的相互作用。这些结果表明，Ku介导的p53 mRNA翻译抑制构成了一种将DNA修复与mRNA翻译联系起来的新机制。
