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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
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
DOI10.1074/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
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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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