Iscience: revealing the mechanism of chemotherapy tolerance related to p53

January 16, 2020 / Biovalley BIOON / -- in the world, more than half of cancer cases are related to p53 gene mutation, and the protein produced by it can protect DNA from inducing cancer changes When the protein is deformed, it will not only lose its protection ability, but also produce new functions, and it will play the role of "traitor", At present, researchers don't know the mechanism of this phenomenon and how it can produce drug resistance Photo source: Guilherme de Oliveira recently published in International Journal iscience In the report above, scientists from the National Institute of structural biology and biological imaging science and technology of Brazil identified a large number of "traitor" proteins in chemoresistant cells derived from glioblastoma, and revealed how these proteins deform to resist therapy, which can form larger agglomerates than healthy individuals, Some of them also have amyloid properties (when mutations induce clumps), which were first observed in the nucleus of living cells in this study The use of living cells is very important for the research in this field In this paper, researchers have identified small oligomers in living cells, which are slightly larger than the healthy version of p53, which will promote the accumulation of p53, and more similar to the situation of human organism It is important that researchers study the p53 specific mutation (m2371) because the original protein without mutation and other mutations do not mediate the same drug tolerance Researchers Lima Silva said they have studied p53 mutations for more than 15 years First, they identified the tendency of proteases to form amyloid aggregates and the key role of different functional forms in cancer development The researchers observed that mutant p53 amyloid aggregates exist in breast cancer, ovarian cancer and prostate cancer Because of their characteristics, how these amyloid aggregates can be a special target of anti-cancer therapy The researchers pointed out that glioblastoma is a kind of malignant, invasive and low survival rate aggressive brain tumor The patients can only survive for 14 months The deformable protein not only participates in the formation of amyloid aggregates, but also has tolerance to temozolomide The researchers hope that the relevant research results can help to develop new therapies for various types of cancer At present, the research It is suggested that misfolded p53 and p53 aggregates may be potential targets for the development of new anticancer therapies Original source: Murilo M pedrite et al, oncogenic gain of function in glioblastoma is linked to mutant p53 amino oligomers, iscience (2020) Doi: 10.1016/j.isci.2020.100820