Mycobacterium tuberculosis suppresses innate immunity by coopting the host ubiquitin system----中国科学院微生物研究所

科研成果

论文题目:	Mycobacterium tuberculosis suppresses innate immunity by coopting the host ubiquitin system
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:	25.566
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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.