Binding of RNA to p53 regulates its oligomerization and DNA-binding activity

Oncogene. 2004 May 27;23(25):4371-9. doi: 10.1038/sj.onc.1207583.

Abstract

The C-terminus of p53 is responsible for maintaining the latent, non-DNA-binding form of p53. However, the mechanism by which the C-terminus regulates DNA binding is not yet fully understood. We show here that p53 interacts with RNA via its C-terminal domain and that disruption of this interaction, by RNase A treatment, truncation or phosphorylation of the C-terminus, restores DNA-binding activity. Furthermore, the oligomerization of p53 is significantly enhanced by disrupting the interaction between p53 and RNA. These findings suggest that binding of RNA to p53 is involved in the mechanism of p53 latency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopolymers
  • Casein Kinase II
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • DNA / metabolism*
  • Dimerization
  • Female
  • Humans
  • Male
  • Neoplasm Proteins / metabolism
  • Phosphorylation
  • Phosphoserine / metabolism
  • Protein Binding / drug effects
  • Protein Processing, Post-Translational
  • Protein Serine-Threonine Kinases / physiology
  • Protein Structure, Tertiary
  • RNA / metabolism*
  • Ribonuclease, Pancreatic / pharmacology
  • Structure-Activity Relationship
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Biopolymers
  • Neoplasm Proteins
  • Tumor Suppressor Protein p53
  • Phosphoserine
  • RNA
  • DNA
  • Casein Kinase II
  • Protein Serine-Threonine Kinases
  • Ribonuclease, Pancreatic
  • Cisplatin