YOD1/TRAF6 association balances p62-dependent IL-1 signaling to NF-κB
- Helmholtz Zentrum München - German Research Center for Environmental Health, Germany
Abstract
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-1κ stimulation, thereby facilitating TRAF6 auto-ubiquitination as well as NEMO/IKKκ 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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Author details
Funding
Deutsche Forschungsgemeinschaft (SPP1365)
- Daniel Krappmann
Wilhelm Sander-Stiftung (2012.075.2)
- Daniel Krappmann
Deutsche Forschungsgemeinschaft (SFB1054 A4)
- Daniel Krappmann
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Schimmack et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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YOD1/TRAF6 association balances p62-dependent IL-1 signaling to NF-κB
eLife 6:e22416.
https://doi.org/10.7554/eLife.22416
