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

Zhaohui Wu, Yuling Shi, Randal S. Tibbetts, Shigeki Miyamoto

Research output: Contribution to journalArticle

363 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1141-1146
Number of pages6
JournalScience
Volume311
Issue number5764
DOIs
StatePublished - Feb 24 2006
Externally publishedYes

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Ataxia Telangiectasia
Phosphotransferases
Serine
Cell Nucleus Active Transport
Double-Stranded DNA Breaks
Ubiquitin
Leucine
Lysine
DNA Damage
Glutamic Acid
Cytoplasm
Transcription Factors
Proteins

All Science Journal Classification (ASJC) codes

  • General

Cite this

Molecular linkage between the kinase ATM and NF-κB signaling in response to genotoxic stimuli. / Wu, Zhaohui; Shi, Yuling; Tibbetts, Randal S.; Miyamoto, Shigeki.

In: Science, Vol. 311, No. 5764, 24.02.2006, p. 1141-1146.

Research output: Contribution to journalArticle

Wu, Zhaohui ; Shi, Yuling ; Tibbetts, Randal S. ; Miyamoto, Shigeki. / Molecular linkage between the kinase ATM and NF-κB signaling in response to genotoxic stimuli. In: Science. 2006 ; Vol. 311, No. 5764. pp. 1141-1146.
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