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P53 Phase separation is crucial towards amyloid aggregation and p63 and p73 have enhanced expression in tumors. This study examines the phase behaviors of p53, p63, and p73. Here we show that unlike the DNA-binding domain of p53 (p53C), the p63C and p73C undergo phase separation, but do not form amyloids under physiological temperatures. Wild-type and mutant p53C form droplets at 4°C and aggregates at 37 °C with amyloid properties. Mutant p53C promotes amyloid-like states in p63C and p73C, recruiting them into membraneless organelles. Amyloid conversion is supported by thioflavin T and Congo red binding, increased light scattering, and circular dichroism. Full-length mutant p53 and p63C (or p73C) co-transfection shows reduced fluorescence recovery after photobleaching. Heparin inhibits the prion-like aggregation of p63C and p73C induced by p53C. These findings highlight the role of p53 in initiating amyloid aggregation in p63 and p73, opening avenues for targeting prion-like conversion in cancer therapy. Phase separation of p53 is crucial in its progression towards amyloid aggregation, while its paralogous forms p63 and p73 have enhanced expression in tumors but reduced aggregation propensity. Here, the authors report the prion-like aggregation of p63 and p73 mediated by p53 and outline that this process can be inhibited by heparin. [ABSTRACT FROM AUTHOR]

Parkinson's disease is a neurological disease in which aggregated forms of the α-synuclein (α-syn) protein are found. We used high hydrostatic pressure (HHP) coupled with NMR spectroscopy to study the dissociation of α-syn fibril into monomers and evaluate their structural and dynamic properties. Different dynamic properties in the non-amyloid-β component (NAC), which constitutes the Greek-key hydrophobic core, and in the acidic C-terminal region of the protein were identified by HHP NMR spectroscopy. In addition, solid-state NMR revealed subtle differences in the HHP-disturbed fibril core, providing clues to how these species contribute to seeding α-syn aggregation. These findings show how pressure can populate so far undetected α-syn species, and they lay out a roadmap for fibril dissociation via pathways not previously observed using other approaches. Pressure perturbs the cavity-prone hydrophobic core of the fibrils by pushing water inward, thereby inducing the dissociation into monomers. Our study offers the molecular details of how hydrophobic interaction and the formation of water-excluded cavities jointly contribute to the assembly and stabilization of the fibrils. Understanding the molecular forces behind the formation of pathogenic fibrils uncovered by pressure perturbation will aid in the development of new therapeutics against Parkinson's disease. [ABSTRACT FROM AUTHOR]