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Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 eLife 2017 ; 6 (ä): ä Nephropedia Template TP
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YOD1/TRAF6 association balances p62-dependent IL-1 signaling to NF-?B #MMPMID28244869
The ubiquitin ligase TRAF6 is a key regulator of canonical I?B kinase (IKK)/NF-?B 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-?B. 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-1? stimulation, thereby facilitating TRAF6 auto-ubiquitination as well as NEMO/IKK? substrate ubiquitination. Further, IL-1 triggered IKK/NF-?B 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-?B.DOI:http://dx.doi.org/10.7554/eLife.22416.001