Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli.
The transcription factor NF-kappaB modulates apoptotic responses induced by genotoxic stress. We show that NF-kappaB essential modulator (NEMO), the regulatory subunit of IkappaB kinase (IKK) (which phosphorylates the NF-kappaB inhibitor IkappaB), 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-kappaB by genotoxic signals.
Mesh Terms:
Active Transport, Cell Nucleus, Adaptor Proteins, Signal Transducing, Amino Acid Motifs, Cell Cycle Proteins, Cell Line, Cell Nucleus, Cytoplasm, DNA Damage, DNA-Binding Proteins, Humans, I-kappa B Kinase, I-kappa B Proteins, NF-kappa B, Nerve Tissue Proteins, Phosphorylation, Protein-Serine-Threonine Kinases, RNA Interference, Recombinant Fusion Proteins, SUMO-1 Protein, Signal Transduction, Tumor Suppressor Proteins, Ubiquitin
Active Transport, Cell Nucleus, Adaptor Proteins, Signal Transducing, Amino Acid Motifs, Cell Cycle Proteins, Cell Line, Cell Nucleus, Cytoplasm, DNA Damage, DNA-Binding Proteins, Humans, I-kappa B Kinase, I-kappa B Proteins, NF-kappa B, Nerve Tissue Proteins, Phosphorylation, Protein-Serine-Threonine Kinases, RNA Interference, Recombinant Fusion Proteins, SUMO-1 Protein, Signal Transduction, Tumor Suppressor Proteins, Ubiquitin
Science
Date: Feb. 24, 2006
PubMed ID: 16497931
View in: Pubmed Google Scholar
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