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

17 Citations (Scopus)

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

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DNA-Activated Protein Kinase
Phosphotransferases
DNA Damage
DNA
Catalytic Domain
S Phase Cell Cycle Checkpoints
Phosphorylation
Catalytic DNA
V(D)J Recombination
JNK Mitogen-Activated Protein Kinases
Glutamine
Serine
Protein Isoforms
Cell Line

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Involvement of DNA-dependent protein kinase in regulation of stress-induced JNK activation. / Park, Su Jung; Oh, Eun Jin; Yoo, Mi Ae; Lee, Suk-Hee.

In: DNA and Cell Biology, Vol. 20, No. 10, 2001, p. 637-645.

Research output: Contribution to journalArticle

Park, Su Jung ; Oh, Eun Jin ; Yoo, Mi Ae ; Lee, Suk-Hee. / Involvement of DNA-dependent protein kinase in regulation of stress-induced JNK activation. In: DNA and Cell Biology. 2001 ; Vol. 20, No. 10. pp. 637-645.
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