The ubiquitin ligase TRIM27 functions as a host restriction factor antagonized by Mycobacterium tuberculosis PtpA during mycobacterial infection.
The ubiquitin ligase TRIM27 functions as a host restriction factor antagonized by Mycobacterium tuberculosis PtpA during mycobacterial infection.
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泛素连接酶 TRIM27 在分枝杆菌感染过程中充当宿主限制因子，被结核分枝杆菌 PtpA 拮抗
DOI：
10.1038/srep34827
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发表时间：
2016-10-04
影响因子：
4.6
通讯作者：
Liu CH
中科院分区：
文献类型：
--
作者：
Wang J;Teng JL;Zhao D;Ge P;Li B;Woo PC;Liu CH
巨噬细胞介导的天然免疫反应在宿主抵御病原体的过程中起着至关重要的作用。近年来，作为限制因素阻止病毒在感染细胞中复制的宿主蛋白呈爆炸式增长。然而，限制结核分枝杆菌(Mtb)的基本因素及其在分枝杆菌感染过程中的调节作用在很大程度上仍不清楚。我们以前报道过Mtb酪氨酸磷酸酶PTPA是一种分泌型效应蛋白，是Mtb在细胞内生存所必需的，它通过选择宿主泛素系统来抑制先天免疫。在这里，我们发现了一种新的与PTPA相互作用的宿主蛋白TRIM27，据报道它具有保守的环区，通常作为一种E3泛素连接酶，干扰各种细胞过程。我们进一步证明了TRIM27通过促进天然免疫反应和细胞凋亡来限制分枝杆菌在巨噬细胞中的存活。有趣的是，Mtb PTPA通过与TRIM27的环区竞争性结合，拮抗TRIM27促进的JNK/p38MAPK通路激活和细胞凋亡。TRIM27可能是Mtb的一个潜在限制因子，其功能被PTPA等Mtb效应蛋白所抵消。我们的研究建议通过靶向TRIM27-PTPA接口来治疗结核病。
Macrophage-mediated innate immune responses play crucial roles in host defense against pathogens. Recent years have seen an explosion of host proteins that act as restriction factors blocking viral replication in infected cells. However, the essential factors restricting Mycobacterium tuberculosis (Mtb) and their regulatory roles during mycobacterial infection remain largely unknown. We previously reported that Mtb tyrosine phosphatase PtpA, a secreted effector protein required for intracellular survival of Mtb, inhibits innate immunity by co-opting the host ubiquitin system. Here, we identified a new PtpA-interacting host protein TRIM27, which is reported to possess a conserved RING domain and usually acts as an E3 ubiquitin ligase that interferes with various cellular processes. We further demonstrated that TRIM27 restricts survival of mycobacteria in macrophages by promoting innate immune responses and cell apoptosis. Interestingly, Mtb PtpA could antagonize TRIM27-promoted JNK/p38 MAPK pathway activation and cell apoptosis through competitively binding to the RING domain of TRIM27. TRIM27 probably works as a potential restriction factor for Mtb and its function is counteracted by Mtb effector proteins such as PtpA. Our study suggests a potential tuberculosis treatment via targeting of the TRIM27-PtpA interfaces.
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DOI：
10.1126/science.1227026
发表时间：
2012-11-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Choy A;Dancourt J;Mugo B;O'Connor TJ;Isberg RR;Melia TJ;Roy CR
通讯作者：
Roy CR
影响因子：
14.9
作者：
Jensen LJ;Kuhn M;Stark M;Chaffron S;Creevey C;Muller J;Doerks T;Julien P;Roth A;Simonovic M;Bork P;von Mering C
通讯作者：
von Mering C
影响因子：
6.4
作者：
Dutta NK;Bandyopadhyay N;Veeramani B;Lamichhane G;Karakousis PC;Bader JS
通讯作者：
Bader JS
影响因子：
44.1
作者：
Lee, James T.;Shan, Jing;Gu, Wei
通讯作者：
Gu, Wei
DOI：
10.1016/j.bbapap.2009.09.008
发表时间：
2010-03-01
影响因子：
3.2
作者：
Chao, Joseph;Wong, Dennis;Av-Gay, Yossef
通讯作者：
Av-Gay, Yossef