Inhibition of p53 protein aggregation as a cancer treatment strategy

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

doi:10.1016/j.cbpa.2022.102230

Inhibition of p53 protein aggregation as a cancer treatment strategy

Curr Opin Chem Biol. 2023 Feb:72:102230. doi: 10.1016/j.cbpa.2022.102230. Epub 2022 Nov 24.

Authors

Kalvin Kwan¹, Omar Castro-Sandoval¹, Christian Gaiddon², Tim Storr³

Affiliations

¹ Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada.
² Inserm UMR_S 1113, Université de Strasbourg, Molecular Mechanisms of Stress Response and Pathologies, Strasbourg, France. Electronic address: gaiddon@unistra.fr.
³ Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada. Electronic address: tim_storr@sfu.ca.

PMID: 36436275
DOI: 10.1016/j.cbpa.2022.102230

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.

Keywords: Aggregation inhibition; Amyloids; Cancer; Reactivation; Small-molecule binding; Zinc; p53 protein.

Publication types

Review

MeSH terms

Amyloid
Humans
Mutation
Neoplasms* / metabolism
Protein Aggregates
Tumor Suppressor Protein p53* / genetics
Tumor Suppressor Protein p53* / metabolism

Substances

Tumor Suppressor Protein p53
Protein Aggregates
Amyloid