Agonist antibody activates death receptor 6 downstream signaling involving TRADD recruitment

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• 作者：Rui Hu ; Qiumei Du ; Xiangyun Yin ; Jingyun Li ; Tingting Wang ; Liguo Zhang
• 关键词：CRD ; cysteine-rich domain ; DD ; death domain ; DR ; death receptor ; FADD ; Fas-associated death domain ; JNK ; c-Jun N-terminal kinase ; N-APP ; N-terminal 尾-amyloid precursor protein ; siRNA ; small interfering RNA ; TNFR ; tumor necrosis factor receptor ; TRADD ; TNFR-associated death domain protein ; TRAF ; tumor necrosis factor receptor-associated factor
• 刊名：FEBS Letters
• 出版年：31 January, 2014
• 年：2014
• 卷：588
• 期：3
• 页码：401-407
• 全文大小：929 K

文摘

Death receptor 6 (DR6) is a member of the death domain-containing receptors that belong to the TNFR superfamily. To date, the ligand for DR6 is still not clearly defined. Here, we developed a functional agonist monoclonal antibody (DQM3) against DR6, which bound to the first cysteine-rich domain. Importantly, DR6 signaling could be clearly activated by DQM3, which was dependent on its intracellular death domain. In addition, we demonstrated that the association between DR6 and TRADD was enhanced upon DQM3 stimulation and TRADD was involved in DR6-induced signaling activation. Taken together, our findings provide new insight into a novel mechanism by which DR6 induces downstream signaling in response to an agonist antibody.