The aggregation of mutant p53 produces prion-like properties in cancer.

摘要: The tumor suppressor protein p53 loses its function in more than 50% of human malignant tumors. Recent studies have suggested that mutant can form aggregates are related to loss-of-function effects, negative dominance and gain-of-function effects cancers with a worsened prognosis. In recent years, several degenerative diseases been shown prion-like properties similar mammalian prion proteins (PrPs). However, whereas rare, the incidence these neurodegenerative pathologies is high. Malignant tumors involving mutated forms seem substrata. aggregation entire three functional domains into amyloid oligomers fibrils has demonstrated. Amyloid detected breast cancer skin Most mutations development found DNA-binding domain (p53C), which experimentally fibrils. Several computation programs corroborated predicted propensity p53C aggregates, some suggest likely globular PrP. Overall, imply exerts dominant-negative regulatory effect on wild-type (WT) when co-aggregating other such as p63, p73 acetyltransferase p300. We review here behavior oncogenic mutants provides an explanation for their high metastatic potential bearing mutations. inhibition oligomeric fibrillar amyloids appears be promising target therapeutic intervention diseases.