TRIM24 facilitates antiviral immunity through mediating K63-linked TRAF3 ubiquitination

Zhu, Qingchen; Yu, Tao; Gan, Shucheng; Wang, Yan; Pei, Yanbo; Zhao, Qifan; Pei, Siyu; Hao, Shumeng; Jia, Yuan; Xu, Jing; Hou, Fanfan; Wu, Xuefeng; Peng, Chao; Wu, Ping; Qin, Jun; Xiao, Yichuan

doi:10.1084/jem.20192083

Cited by 43 publications

(33 citation statements)

References 44 publications

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“…TRAF3 activity and stability are regulated by ubiquitination. Its activation requires K63 ubiquitin conjugation, which is mediated by TRIM24, TRIM35, TRAF3 itself, TRAF6, and other E3 ligases in distinct contexts [ 117 , 144 , 173 , 174 ]. TRIM23 also interacts with TRAF3 in coimmunoprecipitation assay, but the function of TRIM23 in this setting is unknown [ 114 ].…”

Section: Trims In Regulating Prr Signaling Pathways To Ifn-i Produmentioning

confidence: 99%

TRIMming Type I Interferon-Mediated Innate Immune Response in Antiviral and Antitumor Defense

Ning

2021

Viruses

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The tripartite motif (TRIM) family comprises at least 80 members in humans, with most having ubiquitin or SUMO E3 ligase activity conferred by their N-terminal RING domain. TRIMs regulate a wide range of processes in ubiquitination- or sumoylation-dependent manners in most cases, and fewer as adaptors. Their roles in the regulation of viral infections, autophagy, cell cycle progression, DNA damage and other stress responses, and carcinogenesis are being increasingly appreciated, and their E3 ligase activities are attractive targets for developing specific immunotherapeutic strategies for immune diseases and cancers. Given their importance in antiviral immune response, viruses have evolved sophisticated immune escape strategies to subvert TRIM-mediated mechanisms. In this review, we focus on their regulation of IFN-I-mediated innate immune response, which plays key roles in antiviral and antitumor defense.

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Section: Trims In Regulating Prr Signaling Pathways To Ifn-i Produmentioning

confidence: 99%

TRIMming Type I Interferon-Mediated Innate Immune Response in Antiviral and Antitumor Defense

Ning

2021

Viruses

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“… 37 ), depending on the specific context, thereby playing different roles. For instance, K48-linked ubiquitination is responsible for substrate degradation, whereas K63-linked ubiquitination is responsible for downstream signaling activation and protein trafficking 38 . Specifically, cIAPs, an E3 ubiquitin ligase, promotes K48-linked polyubiquitination of TRAF3 for proteasomal degradation, which is a novel mechanism for paricalcitol, a vitamin D receptor agonist, to inhibit inflammation in renal diseases 39 .…”

Section: Discussionmentioning

confidence: 99%

Hypothermic oxygenated perfusion inhibits HECTD3-mediated TRAF3 polyubiquitination to alleviate DCD liver ischemia-reperfusion injury

et al. 2021

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Ischemia-reperfusion injury (IRI) is an inevitable and serious clinical problem in donations after heart death (DCD) liver transplantation. Excessive sterile inflammation plays a fateful role in liver IRI. Hypothermic oxygenated perfusion (HOPE), as an emerging organ preservation technology, has a better preservation effect than cold storage (CS) for reducing liver IRI, in which regulating inflammation is one of the main mechanisms. HECTD3, a new E3 ubiquitin ligase, and TRAF3 have an essential role in inflammation. However, little is known about HECTD3 and TRAF3 in HOPE-regulated liver IRI. Here, we aimed to investigate the effects of HOPE on liver IRI in a DCD rat model and explore the roles of HECTD3 and TRAF3 in its pathogenesis. We found that HOPE significantly improved liver damage, including hepatocyte and liver sinusoidal endothelial cell injury, and reduced DCD liver inflammation. Mechanistically, both the DOC and HECT domains of HECTD3 directly interacted with TRAF3, and the catalytic Cys (C832) in the HECT domain promoted the K63-linked polyubiquitination of TRAF3 at Lys138. Further, the ubiquitinated TRAF3 at Lys138 increased oxidative stress and activated the NF-κB inflammation pathway to induce liver IRI in BRL-3A cells under hypoxia/reoxygenation conditions. Finally, we confirmed that the expression of HECTD3 and TRAF3 was obviously increased in human DCD liver transplantation specimens. Overall, these findings demonstrated that HOPE can protect against DCD liver transplantation-induced-liver IRI by reducing inflammation via HECTD3-mediated TRAF3 K63-linked polyubiquitination. Therefore, HOPE regulating the HECTD3/TRAF3 pathway is a novel target for improving IRI in DCD liver transplantation.

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“…As an innate mechanism to counter viral infection, host performs ubiquitination of viral proteins and targets them for degradation, limiting the viral spread ( Figure 2 ) [ 13 , 14 ]. Various ubiquitin ligases such as TRIM5a (Tripartite motif-containing 5a) [ 15 ], TRIM24 [ 16 ], TRIM33 [ 17 ], TRIM41 [ 18 ], and E6AP, also identified as Ubiquitin-protein ligase (E3A) [ 19 ], are known to ubiquitinate viral proteins. Ubiquitination during viral infection negatively affects the viral replication by:…”

Section: Protein-based Ptmsmentioning

confidence: 99%

Role of Host-Mediated Post-Translational Modifications (PTMs) in RNA Virus Pathogenesis

Kumar

Mehta

Mishra

et al. 2020

IJMS

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Being opportunistic intracellular pathogens, viruses are dependent on the host for their replication. They hijack host cellular machinery for their replication and survival by targeting crucial cellular physiological pathways, including transcription, translation, immune pathways, and apoptosis. Immediately after translation, the host and viral proteins undergo a process called post-translational modification (PTM). PTMs of proteins involves the attachment of small proteins, carbohydrates/lipids, or chemical groups to the proteins and are crucial for the proteins’ functioning. During viral infection, host proteins utilize PTMs to control the virus replication, using strategies like activating immune response pathways, inhibiting viral protein synthesis, and ultimately eliminating the virus from the host. PTM of viral proteins increases solubility, enhances antigenicity and virulence properties. However, RNA viruses are devoid of enzymes capable of introducing PTMs to their proteins. Hence, they utilize the host PTM machinery to promote their survival. Proteins from viruses belonging to the family: Togaviridae, Flaviviridae, Retroviridae, and Coronaviridae such as chikungunya, dengue, zika, HIV, and coronavirus are a few that are well-known to be modified. This review discusses various host and virus-mediated PTMs that play a role in the outcome during the infection.

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TRIM24 facilitates antiviral immunity through mediating K63-linked TRAF3 ubiquitination

Cited by 43 publications

References 44 publications

TRIMming Type I Interferon-Mediated Innate Immune Response in Antiviral and Antitumor Defense

TRIMming Type I Interferon-Mediated Innate Immune Response in Antiviral and Antitumor Defense

Hypothermic oxygenated perfusion inhibits HECTD3-mediated TRAF3 polyubiquitination to alleviate DCD liver ischemia-reperfusion injury

Role of Host-Mediated Post-Translational Modifications (PTMs) in RNA Virus Pathogenesis

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