PDF(Pubmed)
Abstract：
Mutations in the TP53 tumor suppressor gene occur with high prevalence in a wide range of human tumors. A significant fraction of these mutations (around 10%) are nonsense mutations, creating a premature termination codon (PTC) that leads to the expression of truncated inactive p53 protein. Induction of translational readthrough across a PTC in nonsense mutant TP53 allows the production of full-length protein and potentially restoration of normal p53 function. Aminoglycoside antibiotics and a number of novel compounds have been shown to induce full-length p53 in tumor cells carrying various TP53 nonsense mutations. Full-length p53 protein generated by translational readthrough retains the capacity to transactivate p53 target genes and trigger tumor cell death. These findings raise hopes for efficient therapy of TP53 nonsense mutant tumors in the future.
摘要：
TP53抑癌基因的突变在广泛的人类肿瘤中高发。这些突变中有很大一部分（约10％）是无义突变，创建一个过早终止密码子（PTC），导致表达截短的失活p53蛋白。在无义突变体TP53中跨PTC的翻译连读的诱导允许全长蛋白质的产生和潜在的正常p53功能的恢复。氨基糖苷类抗生素和许多新型化合物已显示在携带各种TP53无义突变的肿瘤细胞中诱导全长p53。通过翻译连读产生的全长p53蛋白保留了反式激活p53靶基因并引发肿瘤细胞死亡的能力。这些发现为将来有效治疗TP53无义突变肿瘤带来了希望。
