The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
A Cytoplasmic ATM-TRAF6-cIAP1 Module Links Nuclear DNA Damage Signaling to Ubiquitin-Mediated NF-κB Activation
Open accessAbstract
As part of the genotoxic stress response, cells activate the transcription factor NF-κB. 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 IKKγ SUMOylation. ATM-dependent IKKγ phosphorylation and subsequent ubiquitination were implicated to activate the cytoplasmic IκB 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 IKKγ at K285. Our data indicate that exported SUMOylated IKKγ acts as a substrate. IKKγ monoubiquitination is a prerequisite for genotoxic IKK and NF-κB activation, but also promotes cytokine signaling.
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“Subsequent studies confirmed that following DSB induction, activated ATM couples with a number of protein intermediates leading to its cytoplasmic transport and downstream activation of NF‐kB (Hinz et al, 2010; Wu et al, 2010; Miyamoto, 2011).”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Hinz et al, 2010
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Cites
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Genome maintenance mechanisms for preventing cancer
Hoeijmakers, J. H. J. (2001) · Nature · doi:10.1038/35077232 · Cited by 3,939
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
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Kastan, M. B., & Bartek, J. (2004) · Nature · doi:10.1038/nature03097 · Cited by 2,836
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Poly(ADP-ribose): novel functions for an old molecule
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NF-κB, the first quarter-century: remarkable progress and outstanding questions
Hayden, M. S., & Ghosh, S. (2012) · Genes & Development · doi:10.1101/gad.183434.111 · Cited by 1,693
Tenev, T., Bianchi, K., Darding, M., Broemer, M., Langlais, C., Wållberg, F., Zachariou, A., Lopez, J. S., MacFarlane, M., Cain, K., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.06.006 · Cited by 837
Salminen, A., Kauppinen, A., & Kaarniranta, K. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2011.12.006 · Cited by 763
Dunphy, G., Flannery, S. M., Almine, J. F., Connolly, D. J., Paulus, C., Jønsson, K. L., Jakobsen, M. R., Nevels, M. M., Bowie, A. G., & Unterholzner, L. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.07.034 · Cited by 648
“involves the DNA damage kinase ataxia telangiectasia mutated (ATM) and the enzyme poly(ADP-ribose) polymerase 1 (PARP-1) (Hinz et al., 2010; Piret et al., 1999; Stilmann et al., 2009).”
BackgroundInfluentialThe IκB kinase complex in NF‐κB regulation and beyond
Hinz, M., & Scheidereit, C. (2014) · The EMBO Reports · doi:10.1002/embr.201337983 · Cited by 572
Self-citation
Metadata
- Authors
- Hinz, M., Stilmann, M., Arslan, S. Ç., Khanna, K. K., Dittmar, G., & Scheidereit, C.
- Affiliations
- Max Delbrück Center (DE)
- QIMR Berghofer Medical Research Institute (AU)
- Corresponding author
- Scheidereit, Claus
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 40
- Issue
- 1
- Pages
- 63-74
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2083922442
- Cited by
- 280
- References
- 42
- Citations by year
- 2026: 11 · 2025: 7 · 2024: 17 · 2023: 10 · 2022: 19 · 2021: 21 · 2020: 18 · 2019: 13 · 2018: 16 · 2017: 18 · 2016: 9 · 2015: 12 · 2014: 20 · 2013: 21 · 2012: 44
- FWCI
- 8.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1056 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- ATM kinase, TRAF6, cIAP1, NF-κB activation, DNA damage signaling, genotoxic stress response, PARP1, K63-linked ubiquitination, Ubc13, SUMOylation, PIASy, TAB2, TAK1, IKK complex
- MeSH terms
- Poly (ADP-Ribose) Polymerase-1, MAP Kinase Kinase Kinase 7, Calcium, Cell Nucleus, Cytosol, DNA Damage, DNA-Binding Proteins, HeLa Cells, Humans, Mutation, Phosphorylation, Poly(ADP-ribose) Polymerases, Protein Binding, Recombinant Proteins, Time Factors, Transfection, Tumor Necrosis Factor-alpha, Signal Transduction, NF-kappa B, Protein Serine-Threonine Kinases, Cell Cycle Proteins, MAP Kinase Kinase Kinases, Protein Transport, Tumor Suppressor Proteins, Ubiquitin, RNA Interference, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, TNF Receptor-Associated Factor 6, Adaptor Proteins, Signal Transducing, Inhibitor of Apoptosis Proteins, I-kappa B Kinase, DNA Breaks, Double-Stranded, Ubiquitination, Hep G2 Cells, Ataxia Telangiectasia Mutated Proteins
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