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Schimmack, G. ; Schorpp, K.K. ; Kutzner, K. ; Gehring, T. ; Brenke, J.K. ; Hadian, K. ; Krappmann, D.

YOD1/TRAF6 association balances p62-dependent IL-1 signaling to NF-κB.

eLife 6:e22416 (2017)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The ubiquitin ligase TRAF6 is a key regulator of canonical IκB kinase (IKK)/NF-κB signaling in response to interleukin-1 (IL-1) stimulation. Here, we identified the deubiquitinating enzyme YOD1 (OTUD2) as a novel interactor of TRAF6 in human cells. YOD1 binds to the C-terminal TRAF homology domain of TRAF6 that also serves as the interaction surface for the adaptor p62/Sequestosome-1, which is required for IL-1 signaling to NF-κB. We show that YOD1 competes with p62 for TRAF6 association and abolishes the sequestration of TRAF6 to cytosolic p62 aggregates by a non-catalytic mechanism. YOD1 associates with TRAF6 in unstimulated cells but is released upon IL-1β stimulation, thereby facilitating TRAF6 auto-ubiquitination as well as NEMO/IKKγ substrate ubiquitination. Further, IL-1 triggered IKK/NF-κB signaling and induction of target genes is decreased by YOD1 overexpression and augmented after YOD1 depletion. Hence, our data define that YOD1 antagonizes TRAF6/p62-dependent IL-1 signaling to NF-κB.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Nf-kappab ; Cell Biology ; Human ; Interleukin-1 ; Signal Transduction ; Ubiquitin; Ubiquitin-dependent Kinase; Interacting Protein P62; T-cell-activation; Deubiquitinating Enzyme; Polyubiquitin Chain; Sequestosome 1/p62; Ikk Activation; Traf6; Complex; Interleukin-1
Sprache englisch
Veröffentlichungsjahr 2017
HGF-Berichtsjahr 2017
ISSN (print) / ISBN 2050-084X
e-ISSN 2050-084X
Zeitschrift eLife
Quellenangaben Band: 6, Heft: , Seiten: , Artikelnummer: e22416 Supplement: ,
Verlag eLife Sciences Publications
Verlagsort Cambridge
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
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-509800-002
G-505293-001
PubMed ID 28244869
DOI 10.7554/eLife.22416
WOS ID WOS:000396109000001
Scopus ID 85014923360
Erfassungsdatum 2017-04-20
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