Inhibition of p53 protein aggregation as a cancer treatment strategy.

Kalvin Kwan, Omar Castro-Sandoval, Christian Gaiddon, Tim Storr

Journal: Current opinion in chemical biology 2023;72():102230

PMID: 36436275

Full Text on Elsevier Science View on PubMed

Abstract

The p53 protein plays a critical role in the prevention of genome mutations in the body, however, this protein is frequently mutated in cancer and almost all cancers exhibit malfunction along the p53 pathway. In addition to a loss of activity, mutant p53 protein is prone to unfolding and aggregation, eventually forming amyloid aggregates. There continues to be a considerable effort to develop strategies to restore normal p53 expression and activity and this review details recent advances in small-molecule stabilization of mutant p53 protein and the design of p53 aggregation inhibitors.

Address: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada.; Inserm UMR_S 1113, Université de Strasbourg, Molecular Mechanisms of Stress Response and Pathologies, Strasbourg, France. Electronic address: [email protected].; Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada. Electronic address: [email protected].

DOI: 10.1016/j.cbpa.2022.102230