Molecular Linkage Between the Kinase ATM and NF-κB Signaling in Response to Genotoxic Stimuli
- 24 February 2006
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 311 (5764), 1141-1146
- https://doi.org/10.1126/science.1121513
Abstract
The transcription factor NF-κB modulates apoptotic responses induced by genotoxic stress. We show that NF-κB essential modulator (NEMO), the regulatory subunit of IκB kinase (IKK) (which phosphorylates the NF-κB inhibitor IκB), 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-κB by genotoxic signals.Keywords
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