ATM is Required for IκB Kinase (IKK) Activation in Response to DNA Double Strand Breaks

Nanxin Li, Sharon Banin, Honghai Ouyang, Gloria C. Li, Gilles Courtois, Yosef Shiloh, Michael Karin*, Galit Rotman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

163 Scopus citations


Following challenge with proinflammatory stimuli or generation of DNA double strand breaks (DSBs), transcription factor NF-κB translocates from the cytoplasm to the nucleus to activate expression of target genes. In addition, NF-κB plays a key role in protecting cells from proapoptotic stimuli, including DSBs. Patients suffering from the genetic disorder ataxia-telangiectasia, caused by mutations in the ATM gene, are highly sensitive to inducers of DSBs, such as ionizing radiation. Similar hypersensitivity is displayed by cell lines derived from ataxia-telangiectasia patients or Atm knockout mice. The ATM protein, a member of the phosphatidylinositol 3-kinase (PI3K)-like family, is a multifunctional protein kinase whose activity is stimulated by DSBs. As both ATM and NF-κB deficiencies result in increased sensitivity to DSBs, we examined the role of ATM in NF-κB activation. We report that ATM is essential for NF-κB activation in response to DSBs but not proinflammatory stimuli, and this activity is mediated via the IκB kinase complex. DNA-dependent protein kinase, another member of the PI3K-like family, PI3K itself, and c-Abl, a nuclear tyrosine kinase, are not required for this response.

Original languageEnglish
Pages (from-to)8898-8903
Number of pages6
JournalJournal of Biological Chemistry
Issue number12
StatePublished - 23 Mar 2001


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