| 论文题目: | Mycobacterium tuberculosis suppresses innate immunity by coopting the host ubiquitin system |
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| 作者: | Wang Jing Li Bing-Xi, Ge Pu-Pu, Li Jie, Wang Qi, George Fu Gao*, Qiu Xiao-Bo*, Liu Cui Hua*. |
| 联系作者: | |
| 刊物名称: | Nat Immunol |
| 期: | 16 |
| 卷: | 3 |
| 页: | 237-45 |
| 年份: | 2015 |
| 影响因子: | 23.956 |
| 论文下载: | 下载地址 |
| 摘要: | Mycobacterium tuberculosis PtpA, a secreted tyrosine phosphatase essential for tuberculosis pathogenicity, could be an ideal target for a drug against tuberculosis, but its active-site inhibitors lack selectivity over human phosphatases. Here we found that PtpA suppressed innate immunity dependent on pathways of the kinases Jnk and p38 and the transcription factor NF-kappaB by exploiting host ubiquitin. Binding of PtpA to ubiquitin via a region with no homology to human proteins activated it to dephosphorylate phosphorylated Jnk and p38, leading to suppression of innate immunity. Furthermore, the host adaptor TAB3 mediated NF-kappaB signaling by sensing ubiquitin chains, and PtpA blocked this process by competitively binding the ubiquitin-interacting domain of TAB3. Our findings reveal how pathogens subvert innate immunity by coopting host ubiquitin and suggest a potential tuberculosis treatment via targeting of ubiquitin-PtpA interfaces. |
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