ATM is required for IκB kinase (IKK) activation in response to DNA double strand breaks Journal Article
| Authors: | Li, N.; Banin, S.; Ouyang, H.; Li, G. C.; Courtois, G.; Shiloh, Y.; Karin, M.; Rotman, G. |
| Article Title: | ATM is required for IκB kinase (IKK) activation in response to DNA double strand breaks |
| Abstract: | 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. |
| Keywords: | controlled study; unclassified drug; dna binding protein; gene mutation; human cell; genetics; dna-binding proteins; nonhuman; protein function; cell cycle protein; mouse; animal; metabolism; mouse mutant; animals; cell cycle proteins; mice; mice, knockout; animal tissue; dna damage; gene; apoptosis; cell line; animal experiment; animal model; transcription factor; intracellular transport; immunoglobulin enhancer binding protein; enzyme activation; enzyme inhibitor; enzyme activity; abelson kinase; protein serine threonine kinase; protein tyrosine kinase; phosphatidylinositol 3 kinase; physiology; animalia; dna strand breakage; gene expression regulation; drug antagonism; dna; double stranded dna; genetic engineering; enzyme inhibitors; protein-serine-threonine kinases; tumor suppressor proteins; protein transport; immunoblotting; atm protein; ionizing radiation; protein induction; radiosensitivity; enzyme kinetics; tumor suppressor protein; biochemistry; cell protection; mutagenesis; enzyme assay; knockout mouse; i kappa b kinase; wortmannin; ataxia telangiectasia; cells; atm gene; cell strain; dna dependent protein kinase; i-kappa b kinase; androstadienes; humans; human; priority journal; article; chuk protein, human; ikbkb protein, human; ikbke protein, human; androstane derivative; chuk protein, mouse; ikbkb protein, mouse; ikbke protein, mouse |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 276 |
| Issue: | 12 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2001-03-23 |
| Start Page: | 8898 |
| End Page: | 8903 |
| Language: | English |
| DOI: | 10.1074/jbc.M009809200 |
| PUBMED: | 11114307 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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