Tumor-associated p53 mutations endow cells with malignant phenotypes, including chemoresistance. Amyloid-like oligomers of mutant p53 transform this tumor suppressor into an oncogene. However, the composition and distribution of mutant p53 oligomers are unknown and the mechanism involved in the conversion is sparse. Here, we report accumulation of a p53 mutant within amyloid-like p53 oligomers in glioblastoma-derived cells presenting a chemoresistant gain-of-function phenotype. Statistical analysis from fluorescence fluctuation spectroscopy, pressure-induced measurements, and thioflavin T kinetics demonstrates the distribution of oligomers larger than the active tetrameric form of p53 in the nuclei of living cells and the destabilization of native-drifted p53 species that become amyloid. Collectively, these results provide insights into the role of amyloid-like mutant p53 oligomers in the chemoresistance phenotype of malignant and invasive brain tumors and shed light on therapeutic options to avert cancer.

肿瘤相关的p53突变赋予细胞以恶性表型，包括化学抗性。突变体p53的淀粉样样寡聚物可将这种肿瘤抑制因子转化为癌基因。然而，突变体p53寡聚体的组成和分布是未知的，并且涉及转化的机制是稀疏的。在这里，我们报告胶质母细胞瘤衍生的细胞中的p53突变体淀粉样p53寡聚物内积累，表现出抗化学性的功能获得性表型。来自荧光波动光谱，压力诱导的测量和硫代黄素T动力学的统计分析表明，在活细胞核中寡聚体的分布大于p53的活性四聚体形式，并且不稳定的天然漂移的p53物种变成淀粉样蛋白。总的来说，