Cooperative Roles of Fish Protein Kinase Containing Z-DNA Binding Domains and Double-Stranded RNA-Dependent Protein Kinase in Interferon-Mediated Antiviral Response
文献类型：期刊论文
| 作者 | Liu, Ting-Kai; Zhang, Yi-Bing; Liu, Ying; Sun, Fan; Gui, Jian-Fang |
| 刊名 | JOURNAL OF VIROLOGY
 |
| 出版日期 | 2011-12-01 |
| 卷号 | 85期号:23页码:12769-12780 |
| 关键词 | INNATE IMMUNE-RESPONSE UV-INACTIVATED VIRUS EUKARYOTIC INITIATION-FACTOR-2-ALPHA TYROSINE PHOSPHORYLATION SUBSTRATE RECOGNITION ADENOSINE-DEAMINASE MOLECULAR-CLONING CAB CELLS IN-VIVO PKR |
| ISSN号 | 0022-538X |
| 通讯作者 | Zhang, YB (reprint author), Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Grad Sch, Wuhan 430072, Peoples R China ; ybzhang@ihb.ac.cn ; jfgui@ihb.ac.cn |
| 中文摘要 | The double-stranded RNA (dsRNA)-dependent protein kinase (PKR) inhibits protein synthesis by phosphorylating eukaryotic translation initiation factor 2 alpha (eIF2 alpha). In fish species, in addition to PKR, there exists a PKR-like protein kinase containing Z-DNA binding domains (PKZ). However, the antiviral role of fish PKZ and the functional relationship between fish PKZ and PKR remain unknown. Here we confirmed the coexpression of fish PKZ and PKR proteins in Carassius auratus blastula embryonic (CAB) cells and identified them as two typical interferon (IFN)-inducible eIF2 alpha kinases, both of which displayed an ability to inhibit virus replication. Strikingly, fish IFN or all kinds of IFN stimuli activated PKZ and PKR to phosphorylated eIF2 alpha. Overexpression of both fish kinases together conferred much more significant inhibition of virus replication than overexpression of either protein, whereas morpholino knockdown of both made fish cells more vulnerable to virus infection than knockdown of either. The antiviral ability of fish PKZ was weaker than fish PKR, which correlated with its lower ability to phosphorylate eIF2 alpha than PKR. Moreover, the independent association of fish PKZ or PKR reveals that each of them formed homodimers and that fish PKZ phosphorylated eIF2 alpha independently on fish PKR and vice versa. These results suggest that fish PKZ and PKR play a nonredundant but cooperative role in IFN antiviral response. |
| 英文摘要 | The double-stranded RNA (dsRNA)-dependent protein kinase (PKR) inhibits protein synthesis by phosphorylating eukaryotic translation initiation factor 2 alpha (eIF2 alpha). In fish species, in addition to PKR, there exists a PKR-like protein kinase containing Z-DNA binding domains (PKZ). However, the antiviral role of fish PKZ and the functional relationship between fish PKZ and PKR remain unknown. Here we confirmed the coexpression of fish PKZ and PKR proteins in Carassius auratus blastula embryonic (CAB) cells and identified them as two typical interferon (IFN)-inducible eIF2 alpha kinases, both of which displayed an ability to inhibit virus replication. Strikingly, fish IFN or all kinds of IFN stimuli activated PKZ and PKR to phosphorylated eIF2 alpha. Overexpression of both fish kinases together conferred much more significant inhibition of virus replication than overexpression of either protein, whereas morpholino knockdown of both made fish cells more vulnerable to virus infection than knockdown of either. The antiviral ability of fish PKZ was weaker than fish PKR, which correlated with its lower ability to phosphorylate eIF2 alpha than PKR. Moreover, the independent association of fish PKZ or PKR reveals that each of them formed homodimers and that fish PKZ phosphorylated eIF2 alpha independently on fish PKR and vice versa. These results suggest that fish PKZ and PKR play a nonredundant but cooperative role in IFN antiviral response. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 学科主题 | Virology |
| 类目[WOS] | Virology |
| 研究领域[WOS] | Virology |
| 关键词[WOS] | INNATE IMMUNE-RESPONSE ; UV-INACTIVATED VIRUS ; EUKARYOTIC INITIATION-FACTOR-2-ALPHA ; TYROSINE PHOSPHORYLATION ; SUBSTRATE RECOGNITION ; ADENOSINE-DEAMINASE ; MOLECULAR-CLONING ; CAB CELLS ; IN-VIVO ; PKR |
| 收录类别 | SCI |
| 资助信息 | 973 National Basic Research Program of China[2010CB126301, 2010CB126303]; National Natural Science Foundation of China[30871922]; national transgenic project[2009ZX08010-021B] |
| 语种 | 英语 |
| WOS记录号 | WOS:000296708100063 |
| 公开日期 | 2011-12-22 |
| 源URL | [http://ir.ihb.ac.cn/handle/342005/16437]  |
| 专题 | 水生生物研究所_鱼类生物学及渔业生物技术研究中心_期刊论文 |
| 作者单位 | Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Grad Sch, Wuhan 430072, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Ting-Kai,Zhang, Yi-Bing,Liu, Ying,et al. Cooperative Roles of Fish Protein Kinase Containing Z-DNA Binding Domains and Double-Stranded RNA-Dependent Protein Kinase in Interferon-Mediated Antiviral Response[J]. JOURNAL OF VIROLOGY,2011,85(23):12769-12780. |
| APA | Liu, Ting-Kai,Zhang, Yi-Bing,Liu, Ying,Sun, Fan,&Gui, Jian-Fang.(2011).Cooperative Roles of Fish Protein Kinase Containing Z-DNA Binding Domains and Double-Stranded RNA-Dependent Protein Kinase in Interferon-Mediated Antiviral Response.JOURNAL OF VIROLOGY,85(23),12769-12780. |
| MLA | Liu, Ting-Kai,et al."Cooperative Roles of Fish Protein Kinase Containing Z-DNA Binding Domains and Double-Stranded RNA-Dependent Protein Kinase in Interferon-Mediated Antiviral Response".JOURNAL OF VIROLOGY 85.23(2011):12769-12780. |
入库方式： OAI收割
来源：水生生物研究所
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