SUMOylation Is Required for Optimal TRAF3 Signaling Capacity |
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| Authors: | Sophia Miliara Kalliopi K. Gkouskou Tyson V. Sharp Aristides G. Eliopoulos |
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| Affiliation: | 1. Molecular and Cellular Biology Laboratory, University of Crete School of Medicine, Heraklion, Greece.; 2. Laboratory of Cancer Biology, Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology Hellas, Heraklion, Greece.; 3. Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.; Loyola University Chicago, Stritch School of Medicine, United States of America, |
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| Abstract: | TNF receptor–associated factors (TRAFs) are multifunctional adaptor proteins involved in temporal and spatial coordination of signals necessary for normal immune function. Here, we report that TRAF3, a TRAF family member with a key role in Toll-like and TNF family receptor signaling and suppressor of lymphomagenesis, is post-translationally modified by the small ubiquitin-related modifier (SUMO). Through yeast two-hybrid and co-immunoprecipitation assays we have identified Ubc9, the SUMO conjugating enzyme, as a novel TRAF3-interacting protein. We show that Ubc9-dependent SUMOylation of TRAF3 modulates optimal association with the CD40 receptor, thereby influencing TRAF3 degradation and non-canonical NF-κB activation upon CD40 triggering. Collectively, our findings describe a novel post-translational modification of a TRAF family member and reveal a link between SUMOylation and TRAF-mediated signal transduction. |
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