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Signals from the nucleus: Activation of NF-κB by cytosolic ATM in the DNA damage response.

Sci. Signal. 4:pe2 (2011)
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In response to genotoxic stress induced by DNA double-stranded breaks (DSBs), the inhibitor of κB kinase (IKK) to nuclear factor κB (NF-κB) pathway is activated, which can promote cancer progression and increase the resistance of cancer cells to ionizing radiation or chemotherapeutic drugs. The kinase ataxia telangiectasia mutated (ATM) has a critical role in the activation of NF-κB in response to genotoxic stress. Two reports reveal key cytoplasmic functions of ATM in triggering IKK activation upon DNA damage. After induction of DSBs, ATM is exported from the nucleus and stimulates the ubiquitin ligase activity of tumor necrosis factor receptor-associated factor 6 (TRAF6) or X-linked inhibitor of apoptosis protein, which catalyze the auto-polyubiquitylation of TRAF6 and the polyubiquitylation of the IKK adaptor ELKS, respectively. Ubiquitylation promotes the assembly of signalosomes containing the kinase TAK1 (transforming growth factor b-activated kinase 1). These signalosomes are the site of activation of the cytosolic IKK complex, which stimulates NF-κB-dependent induction of a proliferative and antiapoptotic gene program. These studies show that ATM executes essential functions outside the nucleus in response to DSBs.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Alpha-dependent apoptosis; IKK activation; Genotoxic stress; Kinase; Binding; Linkage; Protein; MALT1; TAB3; TAK1
Sprache englisch
Veröffentlichungsjahr 2011
HGF-Berichtsjahr 2011
ISSN (print) / ISBN 1945-0877
e-ISSN 1937-9145
Zeitschrift Science Signaling
Quellenangaben Band: 4, Heft: 156, Seiten: , Artikelnummer: pe2 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Signaling and Translation (SAT)
Institute of Molecular Toxicology and Pharmacology (TOX)
POF Topic(s) 30203 - Molecular Targets and Therapies
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-509800-002
G-505292-001
G-505293-001
PubMed ID 21245467
Scopus ID 78751554067
Erfassungsdatum 2011-07-27