Identification of a druggable protein-protein interaction site between mutant p53 and its stabilizing chaperone DNAJA1.

ABSTRACT: The TP53 gene is the most frequently mutated gene in human cancers, and the majority of TP53 mutations are missense mutations. As a result, these mutant p53 (mutp53) either directly lose wildtype p53 (wtp53) tumor suppressor function or exhibit a dominant negative effect over wtp53. In addition, some mutp53 have acquired new oncogenic function (gain of function). Therefore, targeting mutp53 for its degradation may serve as a promising strategy for cancer prevention and therapy. Based on our previous finding that farnesylated DNAJA1 is a crucial chaperone in maintaining mutp53 stabilization, and by using an in silico approach, we built 3D homology models of human DNAJA1 and mutp53^R175H proteins, identified the interacting pocket in the DNAJA1-mutp53^R175H complex, and f

SUBMITTER: Tong X 

PROVIDER: S-EPMC7948449 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature