Journal
SCIENCE
Volume 311, Issue 5764, Pages 1141-1146Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1121513
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- NCI NIH HHS [R01-CA77474, R01-CA81065] Funding Source: Medline
- NIGMS NIH HHS [R01-GM067868] Funding Source: Medline
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The transcription factor NF-kappa B modulates apoptotic responses induced by genotoxic stress. We show that NF-kappa B essential modulator (NEMO), the regulatory subunit of I kappa B kinase (IKK) (which phosphorylates the NF-kappa B inhibitor I kappa B), associates with activated ataxia telangiectasia mutated (ATM) after the induction of DNA double-strand breaks. ATM phosphorylates serine-85 of NEMO to promote its ubiquitin-dependent nuclear export. ATM is also exported in a NEMO-dependent manner to the cytoplasm, where it associates with and causes the activation of IKK in a manner dependent on another IKK regulator, a protein rich in glutamate, leucine, lysine, and serine (ELKS). Thus, regulated nuclear shuttling of NEMO links two signaling kinases, ATM and IKK, to activate NF-kappa B by genotoxic signals.
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