• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

USP49 通过去泛素化 MITA 上的 K63 连接泛素化来负调控细胞抗病毒反应。

USP49 negatively regulates cellular antiviral responses via deconjugating K63-linked ubiquitination of MITA.

机构信息

Department of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan, China.

College of Life Sciences, Wuhan University, Wuhan, China.

出版信息

PLoS Pathog. 2019 Apr 3;15(4):e1007680. doi: 10.1371/journal.ppat.1007680. eCollection 2019 Apr.

DOI:10.1371/journal.ppat.1007680
PMID:30943264
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6464240/
Abstract

Mediator of IRF3 activation (MITA, also known as STING and ERIS) is an essential adaptor protein for cytoplasmic DNA-triggered signaling and involved in innate immune responses, autoimmunity and tumorigenesis. The activity of MITA is critically regulated by ubiquitination and deubiquitination. Here, we report that USP49 interacts with and deubiquitinates MITA after HSV-1 infection, thereby turning down cellular antiviral responses. Knockdown or knockout of USP49 potentiated HSV-1-, cytoplasmic DNA- or cGAMP-induced production of type I interferons (IFNs) and proinflammatory cytokines and impairs HSV-1 replication. Consistently, Usp49-/- mice exhibit resistance to lethal HSV-1 infection and attenuated HSV-1 replication compared to Usp49+/+ mice. Mechanistically, USP49 removes K63-linked ubiquitin chains from MITA after HSV-1 infection which inhibits the aggregation of MITA and the subsequent recruitment of TBK1 to the signaling complex. These findings suggest a critical role of USP49 in terminating innate antiviral responses and provide insights into the complex regulatory mechanisms of MITA activation.

摘要

IRF3 激活介体（MITA，也称为 STING 和 ERIS）是细胞质 DNA 触发信号转导所必需的衔接蛋白，参与固有免疫反应、自身免疫和肿瘤发生。MITA 的活性受到泛素化和去泛素化的严格调控。在这里，我们报告说，HSV-1 感染后，USP49 与 MITA 相互作用并使其去泛素化，从而下调细胞抗病毒反应。USP49 的敲低或敲除增强了 HSV-1、细胞质 DNA 或 cGAMP 诱导的 I 型干扰素（IFN）和促炎细胞因子的产生，并损害 HSV-1 复制。一致地，与 Usp49+/+ 小鼠相比，Usp49-/- 小鼠对致死性 HSV-1 感染具有抗性，并且 HSV-1 复制减弱。在机制上，HSV-1 感染后，USP49 从 MITA 上去除 K63 连接的泛素链，从而抑制 MITA 的聚集和随后 TBK1 向信号复合物的募集。这些发现表明 USP49 在终止先天抗病毒反应中起关键作用，并为 MITA 激活的复杂调节机制提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b424/6464240/184d825199ce/ppat.1007680.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b424/6464240/f24906410609/ppat.1007680.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b424/6464240/47d048584dc3/ppat.1007680.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b424/6464240/17d2631342d7/ppat.1007680.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b424/6464240/6043a26a081c/ppat.1007680.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b424/6464240/7c82cd2b8b0a/ppat.1007680.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b424/6464240/184d825199ce/ppat.1007680.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b424/6464240/f24906410609/ppat.1007680.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b424/6464240/47d048584dc3/ppat.1007680.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b424/6464240/17d2631342d7/ppat.1007680.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b424/6464240/6043a26a081c/ppat.1007680.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b424/6464240/7c82cd2b8b0a/ppat.1007680.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b424/6464240/184d825199ce/ppat.1007680.g006.jpg

相似文献

1
USP49 negatively regulates cellular antiviral responses via deconjugating K63-linked ubiquitination of MITA.USP49 通过去泛素化 MITA 上的 K63 连接泛素化来负调控细胞抗病毒反应。
PLoS Pathog. 2019 Apr 3;15(4):e1007680. doi: 10.1371/journal.ppat.1007680. eCollection 2019 Apr.
2
USP20 Promotes Cellular Antiviral Responses via Deconjugating K48-Linked Ubiquitination of MITA.USP20 通过去泛素化 MITA 上的 K48 连接泛素促进细胞抗病毒反应。
J Immunol. 2019 Apr 15;202(8):2397-2406. doi: 10.4049/jimmunol.1801447. Epub 2019 Feb 27.
3
RNF115 plays dual roles in innate antiviral responses by catalyzing distinct ubiquitination of MAVS and MITA.RNF115 在先天抗病毒反应中发挥双重作用，通过催化 MAVS 和 MITA 的不同泛素化。
Nat Commun. 2020 Nov 2;11(1):5536. doi: 10.1038/s41467-020-19318-3.
4
USP13 negatively regulates antiviral responses by deubiquitinating STING.USP13 通过去泛素化 STING 负调控抗病毒反应。
Nat Commun. 2017 May 23;8:15534. doi: 10.1038/ncomms15534.
5
USP44 positively regulates innate immune response to DNA viruses through deubiquitinating MITA.USP44 通过去泛素化 MITA 正向调控先天免疫对 DNA 病毒的反应。
PLoS Pathog. 2020 Jan 22;16(1):e1008178. doi: 10.1371/journal.ppat.1008178. eCollection 2020 Jan.
6
USP18 recruits USP20 to promote innate antiviral response through deubiquitinating STING/MITA.USP18招募USP20通过去泛素化STING/MITA来促进先天性抗病毒反应。
Cell Res. 2016 Dec;26(12):1302-1319. doi: 10.1038/cr.2016.125. Epub 2016 Nov 1.
7
RNF39 facilitates antiviral immune responses by promoting K63-linked ubiquitination of STING.RNF39 通过促进 STING 的 K63 连接泛素化来促进抗病毒免疫反应。
Int Immunopharmacol. 2024 Dec 5;142(Pt A):113091. doi: 10.1016/j.intimp.2024.113091. Epub 2024 Sep 9.
8
ZDHHC11 modulates innate immune response to DNA virus by mediating MITA-IRF3 association.ZDHHC11 通过介导 MITA-IRF3 关联调节先天免疫反应对 DNA 病毒的反应。
Cell Mol Immunol. 2018 Oct;15(10):907-916. doi: 10.1038/cmi.2017.146. Epub 2018 Feb 12.
9
TRIM32 protein modulates type I interferon induction and cellular antiviral response by targeting MITA/STING protein for K63-linked ubiquitination.TRIM32 蛋白通过靶向 MITA/STING 蛋白进行 K63 连接的泛素化来调节 I 型干扰素的诱导和细胞抗病毒反应。
J Biol Chem. 2012 Aug 17;287(34):28646-55. doi: 10.1074/jbc.M112.362608. Epub 2012 Jun 28.
10
RNF26 temporally regulates virus-triggered type I interferon induction by two distinct mechanisms.RNF26通过两种不同机制对病毒触发的I型干扰素诱导进行时间调控。
PLoS Pathog. 2014 Sep 25;10(9):e1004358. doi: 10.1371/journal.ppat.1004358. eCollection 2014 Sep.

引用本文的文献

1
DNA-RNA hybrids in inflammation: sources, immune response, and therapeutic implications.炎症中的DNA-RNA杂交体：来源、免疫反应及治疗意义
J Mol Med (Berl). 2025 May;103(5):511-529. doi: 10.1007/s00109-025-02533-0. Epub 2025 Mar 25.
2
HnRNPC triggers the degradation of MITA to suppress the interferon-mediated antiviral response.异质性核糖核蛋白C（HnRNPC）触发线粒体抗病毒信号蛋白（MITA）的降解以抑制干扰素介导的抗病毒反应。
Vet Res. 2025 Feb 24;56(1):45. doi: 10.1186/s13567-025-01463-6.
3
Type VII secretion system extracellular protein B targets STING to evade host anti- immunity.

本文引用的文献

1
Innate Sensing of DNA Virus Genomes.先天感知 DNA 病毒基因组。
Annu Rev Virol. 2018 Sep 29;5(1):341-362. doi: 10.1146/annurev-virology-092917-043244.
2
USP49 inhibits ischemia-reperfusion-induced cell viability suppression and apoptosis in human AC16 cardiomyocytes through DUSP1-JNK1/2 signaling.USP49 通过 DUSP1-JNK1/2 信号通路抑制缺血再灌注诱导的人 AC16 心肌细胞活力抑制和凋亡。
J Cell Physiol. 2019 May;234(5):6529-6538. doi: 10.1002/jcp.27390. Epub 2018 Sep 24.
3
Cytosolic DNA Sensing in Organismal Tumor Control.机体肿瘤控制中的细胞质 DNA 感应。
VII 型分泌系统细胞外蛋白 B 靶向 STING 以逃避宿主的抗病毒免疫。
Proc Natl Acad Sci U S A. 2024 May 28;121(22):e2402764121. doi: 10.1073/pnas.2402764121. Epub 2024 May 21.
4
MARCH5 promotes STING pathway activation by suppressing polymer formation of oxidized STING.MARCH5 通过抑制氧化 STING 的聚合物形成来促进 STING 途径的激活。
EMBO Rep. 2023 Dec 6;24(12):e57496. doi: 10.15252/embr.202357496. Epub 2023 Nov 2.
5
Deubiquitylating Enzymes in Cancer and Immunity.癌症与免疫中的去泛素化酶
Adv Sci (Weinh). 2023 Dec;10(36):e2303807. doi: 10.1002/advs.202303807. Epub 2023 Oct 27.
6
The Many Ways to Deal with STING.STING 的多种应对方式。
Int J Mol Sci. 2023 May 20;24(10):9032. doi: 10.3390/ijms24109032.
7
Unlocking STING as a Therapeutic Antiviral Strategy.解锁 STING 作为一种治疗性抗病毒策略。
Int J Mol Sci. 2023 Apr 18;24(8):7448. doi: 10.3390/ijms24087448.
8
USP49 deubiquitinase regulates the mitotic spindle checkpoint and prevents aneuploidy.USP49 去泛素化酶调节有丝分裂纺锤体检查点，防止非整倍体。
Cell Death Dis. 2023 Jan 26;14(1):60. doi: 10.1038/s41419-023-05600-x.
9
Current understanding of the cGAS-STING signaling pathway: Structure, regulatory mechanisms, and related diseases.当前对 cGAS-STING 信号通路的理解：结构、调控机制及相关疾病。
Zool Res. 2023 Jan 18;44(1):183-218. doi: 10.24272/j.issn.2095-8137.2022.464.
10
SHP-1 knockdown suppresses mitochondrial biogenesis and aggravates mitochondria-dependent apoptosis induced by all trans retinal through the STING/AMPK pathways.SHP-1 敲低通过 STING/AMPK 通路抑制全反式视黄醛诱导的线粒体生物发生并加重线粒体依赖性细胞凋亡。
Mol Med. 2022 Oct 22;28(1):125. doi: 10.1186/s10020-022-00554-w.
Cancer Cell. 2018 Sep 10;34(3):361-378. doi: 10.1016/j.ccell.2018.05.013. Epub 2018 Jun 28.
4
Detection of Microbial Infections Through Innate Immune Sensing of Nucleic Acids.通过先天免疫感应核酸检测微生物感染
Annu Rev Microbiol. 2018 Sep 8;72:447-478. doi: 10.1146/annurev-micro-102215-095605.
5
The Multifaceted Role of Chromosomal Instability in Cancer and Its Microenvironment.染色体不稳定性在癌症及其微环境中的多方面作用。
Cell. 2018 Sep 6;174(6):1347-1360. doi: 10.1016/j.cell.2018.08.027.
6
Cytoplasmic Mechanisms of Recognition and Defense of Microbial Nucleic Acids.细胞质中识别和防御微生物核酸的机制。
Annu Rev Cell Dev Biol. 2018 Oct 6;34:357-379. doi: 10.1146/annurev-cellbio-100617-062903. Epub 2018 Aug 10.
7
USP49 participates in the DNA damage response by forming a positive feedback loop with p53.USP49 通过与 p53 形成正反馈环参与 DNA 损伤反应。
Cell Death Dis. 2018 May 1;9(5):553. doi: 10.1038/s41419-018-0475-3.
8
Extrinsic Phagocyte-Dependent STING Signaling Dictates the Immunogenicity of Dying Cells.外在吞噬细胞依赖性 STING 信号决定了死亡细胞的免疫原性。
Cancer Cell. 2018 May 14;33(5):862-873.e5. doi: 10.1016/j.ccell.2018.03.027. Epub 2018 Apr 26.
9
Pro-inflammation Associated with a Gain-of-Function Mutation (R284S) in the Innate Immune Sensor STING.先天免疫传感器 STING 中的功能获得性突变（R284S）与促炎反应相关。
Cell Rep. 2018 Apr 24;23(4):1112-1123. doi: 10.1016/j.celrep.2018.03.115.
10
The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer.cGAS-cGAMP-STING 通路将 DNA 损伤与炎症、衰老和癌症联系起来。
J Exp Med. 2018 May 7;215(5):1287-1299. doi: 10.1084/jem.20180139. Epub 2018 Apr 5.