Dual role of p53 amyloid formation in cancer; loss of function and gain of toxicity

摘要: The tumor suppressor p53 plays an important role in genome integrity. It is frequently mutated all types of human cancers, making a key factor cancer progression. Two phenotypic consequences these alterations are dominant; loss function and gain p53, which, several cases, accumulates intracellular aggregates. Although the nature such aggregates still unclear, recent evidence indicates that can undergo conformational transitions leading to amyloid formation. Amyloid diseases, as, Alzheimer's disease, characterized by accumulation insoluble displaying fibrillar conformation. We decided investigate propensity wild type aggregate its consequent assembly into different species, as oligomers fibrils; determine if changes conformation lead p53. Furthermore, we analyzed cases Basal Cell Carcinoma (BCC), for presence amyloids. Here, show forms fibrils, which coincide with inability binding DNA consensus sequences. Both fibrils were detected BCC samples. Additionally, demonstrate most cytotoxic cell cultures. Our study reveals formation demonstrates dual pathogenesis producing protein toxic function, extensively described amyloidogenic diseases. results suggest under certain circumstances, could be considered protein-conformation disease.