p53 phosphorylation in mouse skin and in vitro human skin model by high-dose-radiation exposure.
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.
Koike
Manabu
M
Radiation Hazards Research Group, National Institute of Radiological Sciences, Japan. m_koike@nirs.go.jp
Sugasawa
Jun
J
Koike
Aki
A
Kohno
Yoko
Y
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000502:physiology* / Q000528:radiation effects*; D051379:Mice; D008809:Mice, Inbred C3H; D010766:Phosphorylation / Q000528:radiation effects; D011829:Radiation Dosage; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects*; D014018:Tissue Distribution; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53