p53 Phosphorylation in Mouse Skin and In vitro Human Skin Model by High-dose-radiation Exposure

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  • KOIKE Manabu
    Radiation Hazards Research Group, National Institute of Radiological Sciences
  • SUGASAWA Jun
    Radiation Hazards Research Group, National Institute of Radiological Sciences
  • KOIKE Aki
    Radiation Hazards Research Group, National Institute of Radiological Sciences
  • KOHNO Yoko
    Showa University School of Dentistry

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The skin is an external organ that is most frequently exposed to radiation. High-dose radiation initiates and promotes acute radiation injury. Thus, it is important to investigate the influence of high-dose radiation exposure on the skin at the molecular level. The post-translational modification of p53 plays a central role in radiation responses, including apoptosis and cell growth arrest. Although it is well known that ataxia telangiectasia mutated (ATM) kinase and DNA-dependent protein kinase (DNA-PK) can phosphorylate Ser15/Ser18 of p53 in vitro, the post-translational modification pattern and the modifier of p53 in the skin after exposure to high-dose X-rays are not yet well understood. Here we show that the phosphorylation of p53 on Ser15/Ser18, as well as the phosphorylation of histone H2AX on Ser139, was detected in the keratinocytes of the mouse skin and human skin models after high-dose X-ray irradiation. Following high-dose X-ray irradiation, both proteins were also phosphorylated in the skin keratinocytes of both ATM gene knockout mice and DNA-PK-deficient SCID mice.<br>

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