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Hadian, K. ; Krappmann, D.

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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Open Access Green as soon as Postprint is submitted to ZB.

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Alpha-dependent apoptosis; IKK activation; Genotoxic stress; Kinase; Binding; Linkage; Protein; MALT1; TAB3; TAK1

ISSN (print) / ISBN 1945-0877

e-ISSN 1937-9145

Journal Science Signaling

Quellenangaben Volume: 4, Issue: 156, Article Number: pe2

Publisher American Association for the Advancement of Science (AAAS)

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Research Unit Signaling and Translation (SAT)
Institute of Molecular Toxicology and Pharmacology (TOXI)