Molecular linkage between the kinase ATM and NF-κB signaling in response to genotoxic stimuli

ZH Wu, Y Shi, RS Tibbetts, S Miyamoto - Science, 2006 - science.org
ZH Wu, Y Shi, RS Tibbetts, S Miyamoto
Science, 2006science.org
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 …
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.
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