Involvement of DNA-dependent protein kinase in regulation of stress-induced JNK activation

Su Jung Park, Eun Jin Oh, Mi Ae Yoo, Suk Hee Lee

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

DNA-dependent protein kinase (DNA-PK) is composed of a 460-kDa catalytic subunit and the regulatory subunits Ku70 and Ku80. The complex is activated on DNA damage and plays an essential role in double-strand-break repair and V(D)J recombination. In addition, DNA-PK is involved in S-phase checkpoint arrest following irradiation, although its role in damage-induced checkpoint arrest is not clear. In an effort to understand the role of DNA-PK in damage signaling, human and mouse cells containing the DNA-PK catalytic subunit (DNA-PKcs proficient) were compared with those lacking DNA-PKcs for c-Jun N-terminal kinase (JNK) activity that mediates physiologic responses to DNA damage. The DNA-PKcs-proficient cells showed much tighter regulation of JNK activity after DNA damage, while the level of JNK protein in both cell lines remained unchanged. The JNK proteins physically associated with DNA-PKcs and Ku70/Ku80 heterodimer, and the interaction was significantly stimulated after DNA damage. Various JNK isoforms not only contained a DNA-PK phosphorylation consensus site (serine followed by glutamine) but also were phosphorylated by DNA-PK in vitro. Together, our results suggest that DNA damage induces physical interaction between DNA-PK and JNK, which may in turn negatively affect JNK activity through JNK phosphorylation by DNA-PK.

Original languageEnglish (US)
Pages (from-to)637-645
Number of pages9
JournalDNA and Cell Biology
Volume20
Issue number10
DOIs
StatePublished - Oct 1 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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