Prion protein is required for tumor necrosis factor (tnf)-triggered nuclear factor b (nf-b) signaling and cytokine production
文献类型:期刊论文
作者 | Wu, Gui-Ru1,2; Mu, Tian-Chen3; Gao, Zhen-Xing1; Wang, Jun1; Sy, Man-Sun4; Li, Chao-Yang1,5 |
刊名 | Journal of biological chemistry
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出版日期 | 2017-11-17 |
卷号 | 292期号:46页码:18747-18759 |
关键词 | Deubiquitylation (deubiquitination) Melanoma Nf-b (nf-b) Prion Tumor necrosis factor (tnf) Cyld Nf-b signaling Prp Tnf |
ISSN号 | 0021-9258 |
DOI | 10.1074/jbc.m117.787283 |
通讯作者 | Li, chao-yang(cyli@wh.iov.cn) |
英文摘要 | The expression of normal cellular prion protein (prp) is required for the pathogenesis of prion diseases. however, the physiological functions of prp remain ambiguous. here, we identified prp as being critical for tumor necrosis factor (tnf) -triggered signaling in a human melanoma cell line, m2, and a pancreatic ductal cell adenocarcinoma cell line, bxpc-3. in m2 cells, tnf up-regulates the expression of p-ib-kinase / (p-ikk/), p-p65, and p-jnk, but down-regulates the ib protein, all of which are downstream signaling intermediates in the tnf receptor signaling cascade. when prnp is deleted in m2 cells, the effects of tnf are no longer detectable. more importantly, p-p65 and p-jnk responses are restored when prnp is reintroduced into the prnp null cells. tnf also activates nf-b and increases tnf production in wild-type m2 cells, but not in prp-null m2 cells. similar results are obtained in the bxpc-3 cells. moreover, tnf activation of nf-b requires ubiquitination of receptor-interacting serine/threonine kinase 1 (rip1) and tnf receptor-associated factor 2 (traf2). tnf treatment increases the binding between prp and the deubiquitinase tumor suppressor cylindromatosis (cyld), in these treated cells, binding of cyld to rip1 and traf2 is reduced. we conclude that prp traps cyld, preventing it from binding and deubiquitinating rip1 and traf2. our findings reveal that prp enhances the responses to tnf, promoting proinflammatory cytokine production, which may contribute to inflammation and tumorigenesis. |
WOS关键词 | CARCINOMA CELL-LINE ; KAPPA-B ; FACTOR-ALPHA ; INFLAMMATORY RESPONSE ; EPITHELIAL-CELLS ; PRO-PRION ; ACTIVATION ; CANCER ; BINDING ; MICE |
WOS研究方向 | Biochemistry & Molecular Biology |
WOS类目 | Biochemistry & Molecular Biology |
语种 | 英语 |
WOS记录号 | WOS:000415848000002 |
出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
URI标识 | http://www.irgrid.ac.cn/handle/1471x/2373358 |
专题 | 武汉病毒研究所 |
通讯作者 | Li, Chao-Yang |
作者单位 | 1.Chinese Acad Sci, State Key Lab Virol, Wuhan Inst Virol, 44 Xiao Hong Shan Zhong Qu, Wuhan 430071, Hubei, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100000, Peoples R China 3.Wuhan Univ, Dept Life Sci, Wuhan 430010, Hubei, Peoples R China 4.Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA 5.Wuhan Brain Hosp, 5 Huiji Rd, Wuhan 430010, Hubei, Peoples R China |
推荐引用方式 GB/T 7714 | Wu, Gui-Ru,Mu, Tian-Chen,Gao, Zhen-Xing,et al. Prion protein is required for tumor necrosis factor (tnf)-triggered nuclear factor b (nf-b) signaling and cytokine production[J]. Journal of biological chemistry,2017,292(46):18747-18759. |
APA | Wu, Gui-Ru,Mu, Tian-Chen,Gao, Zhen-Xing,Wang, Jun,Sy, Man-Sun,&Li, Chao-Yang.(2017).Prion protein is required for tumor necrosis factor (tnf)-triggered nuclear factor b (nf-b) signaling and cytokine production.Journal of biological chemistry,292(46),18747-18759. |
MLA | Wu, Gui-Ru,et al."Prion protein is required for tumor necrosis factor (tnf)-triggered nuclear factor b (nf-b) signaling and cytokine production".Journal of biological chemistry 292.46(2017):18747-18759. |
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来源:武汉病毒研究所
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