Enterovirus 71 2b induces cell apoptosis by directly inducing the conformational activation of the proapoptotic protein bax
文献类型:期刊论文
作者 | Cong, Haolong1; Du, Ning1; Yang, Yang1,2; Song, Lei1; Zhang, Wenliang1,2; Tien, Po1 |
刊名 | Journal of virology
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出版日期 | 2016-11-01 |
卷号 | 90期号:21页码:9862-9877 |
ISSN号 | 0022-538X |
DOI | 10.1128/jvi.01499-16 |
通讯作者 | Tien, po(tienpo@sun.im.ac.cn) |
英文摘要 | To survive and replicate within a host, many viruses have evolved strategies that target crucial components within the apoptotic cascade, leading to either inhibition or induction of cell apoptosis. enterovirus 71 (ev71) infections have been demonstrated to impact the mitochondrial apoptotic pathway and induce apoptosis in many cell lines. however, the detailed mechanism of ev71-induced apoptosis remains to be elucidated. in this study, we report that ev71 2b protein (2b) localized to the mitochondria and induced cell apoptosis by interacting directly with and activating the proapoptotic protein bax. 2b recruited bax to the mitochondria and induced bax conformational activation. in addition, mitochondria isolated from 2b-expressing cells that were treated with a recombinant bax showed increased bax interaction and cytochrome c (cyt c) release. importantly, apoptosis in cells with either ev71 infection or 2b expression was dramatically reduced in bax knockdown cells but not in bak knockdown cells, suggesting that bax played a pivotal role in ev71- or 2b-induced apoptosis. further studies indicate that a hydrophobic region of 18 amino acids (aa) in the c-terminal region of 2b (aa 63 to 80) was responsible for the location of 2b in the mitochondria. a hydrophilic region of 14 aa in the n-terminal region of 2b was functional in bax interaction and its subsequent activation. moreover, overexpression of the antiapoptotic protein bcl-x-l abrogates 2b-induced release of cyt c and caspase activation. therefore, this study provides direct evidence that ev71 2b induces cell apoptosis and impacts the mitochondrial apoptotic pathway by directly modulating the redistribution and activation of proapoptotic protein bax. |
WOS关键词 | CYTOCHROME-C RELEASE ; BCL-2 FAMILY-MEMBERS ; MITOCHONDRIA-MEDIATED APOPTOSIS ; PERMEABILITY TRANSITION PORE ; VIRAL HOMOLOGS ; ENDOPLASMIC-RETICULUM ; CLINICAL-FEATURES ; PULMONARY-EDEMA ; MOUTH-DISEASE ; POLIOVIRUS |
WOS研究方向 | Virology |
WOS类目 | Virology |
语种 | 英语 |
WOS记录号 | WOS:000385525700027 |
出版者 | AMER SOC MICROBIOLOGY |
URI标识 | http://www.irgrid.ac.cn/handle/1471x/2374797 |
专题 | 中国科学院大学 |
通讯作者 | Tien, Po |
作者单位 | 1.Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Ctr Mol Virol, Beijing, Peoples R China 2.Chinese Acad Sci, Grad Sch, Beijing, Peoples R China |
推荐引用方式 GB/T 7714 | Cong, Haolong,Du, Ning,Yang, Yang,et al. Enterovirus 71 2b induces cell apoptosis by directly inducing the conformational activation of the proapoptotic protein bax[J]. Journal of virology,2016,90(21):9862-9877. |
APA | Cong, Haolong,Du, Ning,Yang, Yang,Song, Lei,Zhang, Wenliang,&Tien, Po.(2016).Enterovirus 71 2b induces cell apoptosis by directly inducing the conformational activation of the proapoptotic protein bax.Journal of virology,90(21),9862-9877. |
MLA | Cong, Haolong,et al."Enterovirus 71 2b induces cell apoptosis by directly inducing the conformational activation of the proapoptotic protein bax".Journal of virology 90.21(2016):9862-9877. |
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来源:中国科学院大学
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