Prion-like aggregation of mutant p53 in cancer

Trends Biochem Sci. 2014 Jun;39(6):260-7. doi: 10.1016/j.tibs.2014.04.001. Epub 2014 Apr 26.

Abstract

p53 is a master regulatory protein that participates in cellular processes such as apoptosis, DNA repair, and cell cycle control. p53 functions as a homotetrameric tumor suppressor, and is lost in more than 50% of human cancers. Recent studies have suggested that the formation of mutant p53 aggregates is associated with loss-of-function (LoF), dominant-negative (DN), and gain-of-function (GoF) effects. We propose that these phenomena can be explained by a prion-like behavior of mutant p53. We discuss the shared properties of cancer and neurodegenerative diseases and how the prion-like properties of p53 aggregates offer potential targets for drug development.

Keywords: amyloid; cancer; p53; prion; prion-like proteins; protein aggregation.

Publication types

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

MeSH terms

  • Amyloid / chemistry*
  • Animals
  • Humans
  • Mutant Proteins / metabolism*
  • Mutation / genetics*
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Prions / chemistry*
  • Prions / metabolism
  • Protein Multimerization*
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Amyloid
  • Mutant Proteins
  • Prions
  • Tumor Suppressor Protein p53