NF-κB was first identified in 1986 as a B cell-specific transcription factor inducing immunoglobulin κ light chain expression. Subsequent studies revealed that NF-κB plays important roles in development, organogenesis, immunity, inflammation, and neurological functions by spatiotemporally regulating cell proliferation, differentiation, and apoptosis in several cell types. Furthermore, studies on the signal pathways that activate NF-κB led to the discovery of TRAF family proteins with E3 ubiquitin ligase activity, which function downstream of the receptor. This discovery led to the proposal of an entirely new signaling mechanism concept, wherein K63-ubiquitin chains act as a scaffold for the signaling complex to activate downstream kinases. This concept has revolutionized ubiquitin studies by revealing the importance of the nonproteolytic functions of ubiquitin not only in NF-κB signaling but also in a variety of other biological systems. TRAF6 is the most diverged among the TRAF family proteins, and our studies uncovered its notable physiological and pathological functions.

NF-κB 于 1986 年首次被鉴定为诱导免疫球蛋白 κ 轻链表达的 B 细胞特异性转录因子。随后的研究表明，NF-κB 通过时空调节多种细胞类型的细胞增殖、分化和凋亡，在发育、器官发生、免疫、炎症和神经功能中发挥重要作用。此外，对激活 NF-κB 信号通路的研究发现了具有 E3 泛素连接酶活性的 TRAF 家族蛋白，该蛋白在受体下游发挥作用。这一发现提出了一种全新的信号传导机制概念，其中 K63-泛素链充当信号传导复合物的支架，以激活下游激酶。这一概念揭示了泛素非蛋白水解功能不仅在 NF-κB 信号转导中而且在各种其他生物系统中的重要性，彻底改变了泛素研究。 TRAF6是TRAF家族蛋白中差异最大的，我们的研究揭示了其显着的生理和病理功能。