title: Agonist antibody activates death receptor 6 downstream signaling involving TRADD recruitment.
abstract: 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.
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Hu
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Qiumei
authors.initials: Q
authors.lastname: Du
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xiangyun
authors.initials: X
authors.lastname: Yin
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology, General Hospital of PLA Shenyang Military Area Command, Shenyang 110015, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: liguozhang@ibp.ac.cn.
authors.forename: Liguo
authors.initials: L
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D053199:TNF Receptor-Associated Death Domain Protein / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D053199:TNF Receptor-Associated Death Domain Protein; C114109:TNFRSF21 protein, human; D014409:Tumor Necrosis Factor-alpha
keywords: Agonist antibody; CRD; DD; DR; DR6; Death domain; FADD; Fas-associated death domain; JNK; N-APP; N-terminal β-amyloid precursor protein; TNFR; TNFR-associated death domain protein; TRADD; TRAF; c-Jun N-terminal kinase; cysteine-rich domain; death domain; death receptor; siRNA; small interfering RNA; tumor necrosis factor receptor; tumor necrosis factor receptor-associated factor