Miliara Sophia, Gkouskou Kalliopi K, Sharp Tyson V, Eliopoulos Aristides G
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.
PLoS One. 2013 Nov 18;8(11):e80470. doi: 10.1371/journal.pone.0080470. eCollection 2013.
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.
肿瘤坏死因子受体相关因子（TRAFs）是多功能衔接蛋白，参与正常免疫功能所需信号的时空协调。在此，我们报告TRAF3，一种在Toll样受体和肿瘤坏死因子家族受体信号传导以及淋巴瘤发生抑制中起关键作用的TRAF家族成员，会被小泛素相关修饰物（SUMO）进行翻译后修饰。通过酵母双杂交和免疫共沉淀实验，我们鉴定出SUMO缀合酶Ubc9是一种新的与TRAF3相互作用的蛋白。我们表明，TRAF3的Ubc9依赖性SUMO化调节与CD40受体的最佳结合，从而影响CD40触发时TRAF3的降解和非经典NF-κB激活。总体而言，我们的研究结果描述了TRAF家族成员一种新的翻译后修饰，并揭示了SUMO化与TRAF介导的信号转导之间的联系。
