Unidad de Investigación, Hospital Universitario de Canarias, Instituto de Tecnologias Biomedicas, Tenerife, Spain.
Cell Cycle. 2012 Feb 15;11(4):715-20. doi: 10.4161/cc.11.4.19154.
Tight regulation of p53 is essential for its central role in maintaining genome stability and tumor prevention. Here, EDD/ UBR5/hHyd, hereafter called EDD, is identified as a novel regulator of p53. Downregulation of EDD results in elevated p53 protein levels both in transformed and untransformed cells. Concomitant with a rise in p53, the levels of p21, a critical p53 target, are also elevated in these conditions. Surprisingly, EDD knockdown does not affect p53 protein stability, and p53 mRNA levels do not increase significantly upon EDD depletion. Consistent with the function of p53, EDD downregulation triggers a senescent phenotype in fibroblasts at later time points. In addition, the increased p53 levels upon EDD depletion cause a G(1) arrest, as co-depletion of EDD and p53 completely rescues this effect on cell cycle progression.
p53 的严格调控对于其在维持基因组稳定性和预防肿瘤中的核心作用至关重要。在这里，EDD/UBR5/hHyd（以下简称 EDD）被鉴定为 p53 的一种新型调节因子。EDD 的下调导致转化和未转化细胞中 p53 蛋白水平升高。伴随着 p53 的增加，p53 的关键靶标 p21 的水平也在这些条件下升高。令人惊讶的是，EDD 敲低并不影响 p53 蛋白稳定性，并且在 EDD 耗尽时 p53 mRNA 水平没有显著增加。与 p53 的功能一致，EDD 下调在稍后的时间点在成纤维细胞中引发衰老表型。此外，EDD 耗尽时增加的 p53 水平导致 G1 期阻滞，因为 EDD 和 p53 的共耗尽完全挽救了对细胞周期进程的这种影响。
