ATM activation by a sulfhydryl-reactive inflammatory cyclopentenone prostaglandin

Masahiko Kobayashi, Hirohito Ono, Keiko Mihara, Hiroshi Tauchi, Kenshi Komatsu, Takashi Shibata, Hiroko Shimizu, Koji Uchida, Ken Ichi Yamamoto

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


ATM (ataxia-telangiectasia mutated) is activated by a variety of noxious agent, including oxidative stress, and ATM deficiency results in an anomalous cellular response to oxidative stress. However, the mechanisms for ATM activation by oxidative stress remain to be established. Furthermore, it is not clear whether ATM responds to oxidative DNA damage or to a change in the intracellular redox state, independent of DNA damage. We found that ATM is activated by N-methyl-N′-nitro-nitrosoguanidine (MNNG) and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), in NBS1- or MSH6-deficient cells. We further found that ATM is activated by treating chromatin-free immunoprecipitated ATM with MNNG or 15d-PGJ2, which modifies free sulfhydryl (SH) groups, and that 15d-PGJ2 binds covalently to ATM. Interestingly, 15d-PGJ2-induced ATM activation leads to p53 activation and apoptosis, but not to Chk2 or H2AX phosphorylation. These results indicate that ATM is activated through the direct modification of its SH groups, independent of DNA damage, and this activation leads, downstream, to apoptosis.

Original languageEnglish
Pages (from-to)779-789
Number of pages11
JournalGenes to Cells
Issue number7
Publication statusPublished - Jul 2006
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Cell Biology


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