title: SUMOylation is required for optimal TRAF3 signaling capacity.
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.
authors.affiliation: Molecular and Cellular Biology Laboratory, University of Crete School of Medicine, Heraklion, Greece ; Laboratory of Cancer Biology, Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology Hellas, Heraklion, Greece.
authors.forename: Sophia
authors.initials: S
authors.lastname: Miliara
authors.forename: Kalliopi K
authors.initials: KK
authors.lastname: Gkouskou
authors.forename: Tyson V
authors.initials: TV
authors.lastname: Sharp
authors.forename: Aristides G
authors.initials: AG
authors.lastname: Eliopoulos
mesh_terms: D019013:CD40 Antigens / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D006801:Humans; D008223:Lymphoma / Q000378:metabolism; D052003:NF-kappa B p52 Subunit / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping / Q000379:methods; D059748:Proteolysis; D015398:Signal Transduction; D058207:Sumoylation; D048008:TNF Receptor-Associated Factor 3 / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D019013:CD40 Antigens; D052003:NF-kappa B p52 Subunit; D048008:TNF Receptor-Associated Factor 3; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9