p53-R273 oncogenic mutations

Variable Mutations at the p53-R273 Oncogenic Hotspot Position Leads to Altered Properties

Variable Mutations at the p53-R273 Oncogenic Hotspot Position Leads to Altered Properties

This work stems from an interesting observation that genetic mutations result in the switching of one amino acid to different variants at the same codon show different cancer pathogenesis. We are trying to comprehend the molecular mechanism for the variation in gain-of-function opted by these variants. Several complementary experiments aided with computational studies show that residue-specific mechanism of unfolding and self-assembly of the entire protein might be one of the crucial parameters for their different oncogenic traits. These studies thus call for the need for developing therapeutic strategies that consider the resultant mutant-variant as a target rather than a mutation position. This is an important lead towards the understanding of the molecular contribution of p53 mutant aggregation in cancer.

(Biophys. J. Volume 118, Issue 3, 2020, Pages 720-728, https://doi.org/10.1016/j.bpj.2019.12.015 )