The molecular mechanism of temperature-dependent p53C phase separation accelerated by oncogenic mutations: insights from all-atom and coarse-grained molecular dynamics simulations
Abstract
, 15 °C and 37 °C) compared to the wild type by increasing solvent exposure of aggregation-prone segments and altering crucial inter-interactions. In contrast, R249S mutation resulted in greater water retention, along with the emergence of independent spherical aggregates. These results provide mechanistic insights into how M237I and R249S mutations promote temperature-dependent liquid-liquid phase separation (LLPS) and subsequent aggregation of p53C, suggesting promising avenues for anticancer therapeutic strategies that target phase separation-driven oncogenesis.
Fields of Study & Subjects
Cancer-related Molecular Pathways
RNA Research and Splicing
DNA Repair Mechanisms
Publication details
- Journal / source
- Physical Chemistry Chemical Physics
- Publisher
- Royal Society of Chemistry (RSC)
- Volume
- 28
- Issue
- 6
- Pages
- 4277–4288
- Publication date
- 1 January 2026
- Language
- EN