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

Shingo Komiyama, Sachiko Taniguchi, Yoshihisa Matsumoto, Eri Tsunoda, Takayo Ohto, Yuka Suzuki, Hong Lan Yin, Masanori Tomita, Atsushi Enomoto, Akinori Morita, Takahiko Suzuki, Kuni Ohtomo, Yoshio Hosoi, Norio Suzuki

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18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)816-822
Number of pages7
JournalBiochemical and biophysical research communications
Volume323
Issue number3
DOIs
Publication statusPublished - 2004 Oct 22
Externally publishedYes

Keywords

  • Ataxia-telangiectasia mutated
  • DNA double-strand break
  • DNA-dependent protein kinase
  • Ionizing radiation
  • Phosphorylation
  • p53

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Komiyama, S., Taniguchi, S., Matsumoto, Y., Tsunoda, E., Ohto, T., Suzuki, Y., Yin, H. L., Tomita, M., Enomoto, A., Morita, A., Suzuki, T., Ohtomo, K., Hosoi, Y., & Suzuki, N. (2004). Potentiality of DNA-dependent protein kinase to phosphorylate Ser46 of human p53. Biochemical and biophysical research communications, 323(3), 816-822. https://doi.org/10.1016/j.bbrc.2004.08.161