Prion-like p53 Amyloids in Cancer

Biochemistry. 2020 Jan 21;59(2):146-155. doi: 10.1021/acs.biochem.9b00796. Epub 2019 Oct 21.


The global transcription factor, p53, is a master regulator of gene expression in cells. Mutations in the TP53 gene promote unregulated cell growth through the inactivation of downstream effectors of the p53 pathway. In fact, mutant p53 is highly prone to misfolding and frequently resides inside the cell as large aggregates, causing loss of physiological function of the tumor-suppressor protein. Here, we review the plausible reasons for functional loss of p53, including amyloid formation leading to unhindered cancer progression. We discuss previous as well as recent findings regarding the amyloid formation of p53 in vitro and in vivo. We elaborate on prion-like properties of p53 amyloids and their possible involvement in cancer progression. Because the p53 pathway is historically most targeted for the development of anticancer therapeutics, we have also summarized some of the recent approaches and advances in reviving the antiproliferative activities of wild-type p53. In this Perspective, we provide insight into understanding p53 as a prion-like protein and propose cancer to be recognized as an amyloid or prion-like disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyloidogenic Proteins / drug effects
  • Amyloidogenic Proteins / metabolism*
  • Animals
  • Antineoplastic Agents / therapeutic use
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / etiology*
  • Protein Aggregates / drug effects
  • Protein Conformation / drug effects
  • Protein Multimerization / drug effects
  • Tumor Suppressor Protein p53 / drug effects
  • Tumor Suppressor Protein p53 / metabolism*


  • Amyloidogenic Proteins
  • Antineoplastic Agents
  • Protein Aggregates
  • Tumor Suppressor Protein p53