![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
| Item Type: | Article |
|---|---|
| Title: | A cytoplasmic ATM-TRAF6-cIAP1 module links nuclear DNA damage signaling to ubiquitin-mediated NF-κB activation |
| Creators Name: | Hinz, M., Stilmann, M., Coel Arslan, S., Khanna, K.K., Dittmar, G. and Scheidereit, C. |
| Abstract: | 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. |
| Keywords: | Signal Transducing Adaptor Proteins, Calcium, Cell Cycle Proteins, Cell Nucleus, Cytosol, Double-Stranded DNA Breaks, DNA Damage, DNA-Binding Proteins, Hela Cells, Hep G2 Cells, IκB Kinase, Inhibitor of Apoptosis Proteins, MAP Kinase Kinase Kinases, Mutation, NF-κB, Phosphorylation, Poly(ADP-ribose) Polymerases, Protein Binding, Protein Transport, Protein-Serine-Threonine Kinases, RNA Interference, Recombinant Proteins, Signal Transduction, TNF Receptor-Associated Factor 6, Time Factors, Transfection, Tumor Necrosis Factor-α, Tumor Suppressor Proteins, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitination |
| Source: | Molecular Cell |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Volume: | 40 |
| Number: | 1 |
| Page Range: | 63-74 |
| Date: | 8 October 2010 |
| Official Publication: | https://doi.org/10.1016/j.molcel.2010.09.008 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
