Potentiality of DNA-dependent protein kinase to phosphorylate Ser46 of human p53

Biochem Biophys Res Commun. 2004 Oct 22;323(3):816-22. doi: 10.1016/j.bbrc.2004.08.161.


DNA damage induces accumulation and activation of p53 via various posttranslational modifications. Among them, several lines of evidence indicated the phosphorylation of Ser46 as an important mediator of DNA damage-induced apoptosis but the responsible kinase remains to be clarified, especially in the case of ionizing radiation (IR). Here we showed that DNA-dependent protein kinase (DNA-PK) could phosphorylate Ser46 of p53 in addition to reported phosphorylation sites Ser15 and Ser37. However, IR-induced phosphorylation of Ser46 was seen even in M059J, a human glioma cell line lacking DNA-PKcs, and it was, at most, only slightly less than in control M059K. On the other hand, a related kinase ataxia-telangiectasia mutated (ATM), which was shown to be essential for IR-induced phosphorylation of Ser46, could poorly phosphorylate Ser46 by itself. These results collectively suggested two pathways for IR-induced phosphorylation of Ser46, i.e., direct phosphorylation by DNA-PK and indirect phosphorylation via ATM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Line, Tumor / enzymology
  • Cell Line, Tumor / radiation effects
  • DNA / chemistry*
  • DNA / metabolism*
  • DNA / radiation effects
  • DNA Damage*
  • DNA-Activated Protein Kinase
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Nuclear Proteins
  • Phosphorylation / radiation effects
  • Protein Binding
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / metabolism*
  • Serine / chemistry
  • Serine / metabolism*
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / metabolism*


  • DNA-Binding Proteins
  • Nuclear Proteins
  • Tumor Suppressor Protein p53
  • Serine
  • DNA
  • DNA-Activated Protein Kinase
  • PRKDC protein, human
  • Protein-Serine-Threonine Kinases