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Agonist antibody activates death receptor 6 downstream signaling involving TRADD recruitment
Author(s) -
Hu Rui,
Du Qiumei,
Yin Xiangyun,
Li Jingyun,
Wang Tingting,
Zhang Liguo
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.12.010
Subject(s) - tradd , agonist , microbiology and biotechnology , signal transduction , death domain , receptor , chemistry , monoclonal antibody , antibody , immunology , programmed cell death , biology , biochemistry , apoptosis
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.