VRK1 interacts with p53 forming a basal complex that is activated by UV-induced DNA damage

FEBS Lett. 2014 Mar 3;588(5):692-700. doi: 10.1016/j.febslet.2014.01.040. Epub 2014 Jan 31.

Abstract

DNA damage immediate cellular response requires the activation of p53 by kinases. We found that p53 forms a basal stable complex with VRK1, a Ser-Thr kinase that responds to UV-induced DNA damage by specifically phosphorylating p53. This interaction takes place through the p53 DNA binding domain, and frequent DNA-contact mutants of p53, such as R273H, R248H or R280K, do not disrupt the complex. UV-induced DNA damage activates VRK1, and is accompanied by phosphorylation of p53 at Thr-18 before it accumulates. We propose that the VRK1-p53 basal complex is an early-warning system for immediate cellular responses to DNA damage.

Keywords: DNA damage; Interaction; Phosphorylation; Vaccinia-related kinase 1; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DNA Damage*
  • DNA Repair
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mutation, Missense
  • Phosphorylation
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Interaction Maps
  • Protein Multimerization
  • Protein Processing, Post-Translational
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Stability
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Ultraviolet Rays

Substances

  • Intracellular Signaling Peptides and Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Protein Serine-Threonine Kinases
  • VRK1 protein, human