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Verheugd, P.* ; Forst, A.H.* ; Milke, L.* ; Herzog, N.* ; Feijs, K.L.H.* ; Kremmer, E. ; Kleine, H.* ; Lüscher, B.*

Regulation of NF-κB signalling by the mono-ADP-ribosyltransferase ARTD10.

Nat. Commun. 4:1683 (2013)
Verlagsversion DOI PMC
Open Access Gold
Adenosine diphosphate-ribosylation is a post-translational modification mediated by intracellular and membrane-associated extracellular enzymes and many bacterial toxins. The intracellular enzymes modify their substrates either by poly-ADP-ribosylation, exemplified by ARTD1/PARP1, or by mono-ADP-ribosylation. The latter has been discovered only recently, and little is known about its physiological relevance. The founding member of mono-AD-Pribosyltransferases is ARTD10/PARP10. It possesses two ubiquitin-interaction motifs, a unique feature among ARTD/PARP enzymes. Here, we find that the ARTD10 ubiquitin-interaction motifs bind to K63-linked poly-ubiquitin, a modification that is essential for NF-kappa B signalling. We therefore studied the role of ARTD10 in this pathway. ARTD10 inhibits the activation of NF-kB and downstream target genes in response to interleukin-1 beta and tumour necrosis factor-a, dependent on catalytic activity and poly-ubiquitin binding of ARTD10. Mechanistically ARTD10 interferes with poly-ubiquitination of NEMO, which interacts with and is a substrate of ARTD10. Our findings identify a novel regulator of NF-kB signalling and provide evidence for cross-talk between K63-linked poly-ubiquitination and mono-ADP-ribosylation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter UBIQUITIN-BINDING; ACTIVATION; PROTEIN; POLY(ADP-RIBOSE); IDENTIFICATION; DEGRADATION; MECHANISMS; GENE; PHOSPHORYLATION; RIBOSYLATION
Sprache englisch
Veröffentlichungsjahr 2013
HGF-Berichtsjahr 2013
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 4, Heft: , Seiten: , Artikelnummer: 1683 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501793-001
PubMed ID 23575687
Scopus ID 84877724803
Erfassungsdatum 2013-06-28