Activation of the ATM kinase by ionizing radiation and phosphorylation of p53

Science. 1998 Sep 11;281(5383):1677-9. doi: 10.1126/science.281.5383.1677.

Abstract

The p53 tumor suppressor protein is activated and phosphorylated on serine-15 in response to various DNA damaging agents. The gene product mutated in ataxia telangiectasia, ATM, acts upstream of p53 in a signal transduction pathway initiated by ionizing radiation. Immunoprecipitated ATM had intrinsic protein kinase activity and phosphorylated p53 on serine-15 in a manganese-dependent manner. Ionizing radiation, but not ultraviolet radiation, rapidly enhanced this p53-directed kinase activity of endogenous ATM. These observations, along with the fact that phosphorylation of p53 on serine-15 in response to ionizing radiation is reduced in ataxia telangiectasia cells, suggest that ATM is a protein kinase that phosphorylates p53 in vivo.

Publication types

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

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins
  • Cell Line
  • DNA Damage
  • DNA-Activated Protein Kinase
  • DNA-Binding Proteins*
  • Enzyme Activation
  • Humans
  • Lymphocytes / metabolism
  • Lymphocytes / radiation effects
  • Mutation
  • Nuclear Proteins
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Phosphoserine / metabolism
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism
  • Proteins / genetics
  • Proteins / metabolism*
  • Radiation, Ionizing*
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Transfection
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Proteins
  • Ultraviolet Rays

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Proteins
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Phosphoserine
  • Protein Kinases
  • Phosphatidylinositol 3-Kinases
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • DNA-Activated Protein Kinase
  • PRKDC protein, human
  • Protein-Serine-Threonine Kinases