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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2010-10-11
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pubmed:abstractText |
As part of the genotoxic stress response, cells activate the transcription factor NF-?B. The DNA strand break sensor poly(ADP-ribose)-polymerase-1 (PARP-1) and the kinase ataxia telangiectasia mutated (ATM) act as proximal signal mediators. PARP-1 assembles a nucleoplasmic signalosome, which triggers PIASy-mediated IKK? SUMOylation. ATM-dependent IKK? phosphorylation and subsequent ubiquitination were implicated to activate the cytoplasmic I?B kinase (IKK) complex by unknown mechanisms. We show that activated ATM translocates in a calcium-dependent manner to cytosol and membrane fractions. Through a TRAF-binding motif, ATM activates TRAF6, resulting in Ubc13-mediated K63-linked polyubiquitin synthesis and cIAP1 recruitment. The ATM-TRAF6-cIAP1 module stimulates TAB2-dependent TAK1 phosphorylation. Both nuclear PARP-1- and cytoplasmic ATM-driven signaling branches converge at the IKK complex to catalyze monoubiquitination of IKK? at K285. Our data indicate that exported SUMOylated IKK? acts as a substrate. IKK? monoubiquitination is a prerequisite for genotoxic IKK and NF-?B activation, but also promotes cytokine signaling.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/BIRC2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/MAP kinase kinase kinase 7,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/PARP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TAB2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TNF Receptor-Associated Factor 6,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/UBE2N protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Conjugating Enzymes,
http://linkedlifedata.com/resource/pubmed/chemical/ataxia telangiectasia mutated...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1097-4164
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pubmed:author |
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
8
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
63-74
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:20932475-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:20932475-Calcium,
pubmed-meshheading:20932475-Cell Cycle Proteins,
pubmed-meshheading:20932475-Cell Nucleus,
pubmed-meshheading:20932475-Cytosol,
pubmed-meshheading:20932475-DNA Breaks, Double-Stranded,
pubmed-meshheading:20932475-DNA Damage,
pubmed-meshheading:20932475-DNA-Binding Proteins,
pubmed-meshheading:20932475-HeLa Cells,
pubmed-meshheading:20932475-Hep G2 Cells,
pubmed-meshheading:20932475-Humans,
pubmed-meshheading:20932475-I-kappa B Kinase,
pubmed-meshheading:20932475-Inhibitor of Apoptosis Proteins,
pubmed-meshheading:20932475-MAP Kinase Kinase Kinases,
pubmed-meshheading:20932475-Mutation,
pubmed-meshheading:20932475-NF-kappa B,
pubmed-meshheading:20932475-Phosphorylation,
pubmed-meshheading:20932475-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:20932475-Protein Binding,
pubmed-meshheading:20932475-Protein Transport,
pubmed-meshheading:20932475-Protein-Serine-Threonine Kinases,
pubmed-meshheading:20932475-RNA Interference,
pubmed-meshheading:20932475-Recombinant Proteins,
pubmed-meshheading:20932475-Signal Transduction,
pubmed-meshheading:20932475-TNF Receptor-Associated Factor 6,
pubmed-meshheading:20932475-Time Factors,
pubmed-meshheading:20932475-Transfection,
pubmed-meshheading:20932475-Tumor Necrosis Factor-alpha,
pubmed-meshheading:20932475-Tumor Suppressor Proteins,
pubmed-meshheading:20932475-Ubiquitin,
pubmed-meshheading:20932475-Ubiquitin-Conjugating Enzymes,
pubmed-meshheading:20932475-Ubiquitination
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pubmed:year |
2010
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pubmed:articleTitle |
A cytoplasmic ATM-TRAF6-cIAP1 module links nuclear DNA damage signaling to ubiquitin-mediated NF-?B activation.
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pubmed:affiliation |
Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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