Regulation of MDA5-MAVS Antiviral Signaling Axis by TRIM25 through TRAF6-Mediated NF-κB Activation

Lee, Na-Rae; Kim, Hyein; Choi, Myung-Soo; Yi, Chae-Min; Inn, Kyung‐Soo

doi:10.14348/molcells.2015.0047

Cited by 43 publications

(36 citation statements)

References 23 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TRIM25 acts as an E3 ubiquitin ligase in both MAVS ubiquitination and degradation (45). TRIM25 is also required for full NF-B activation by ubiquitinating TRAF6 (46). Targeting TRIM25 is an efficient approach to inhibit the IFN signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination

Hu¹,

Li²,

Gao³

et al. 2017

J Virol

272

315

View full text Add to dashboard Cite

Severe acute respiratory syndrome (SARS) is a respiratory disease, caused by a coronavirus (SARS-CoV), that is characterized by atypical pneumonia. The nucleocapsid protein (N protein) of SARS-CoV plays an important role in inhibition of type I interferon (IFN) production via an unknown mechanism. In this study, the SARS-CoV N protein was found to bind to the SPRY domain of the tripartite motif protein 25 (TRIM25) E3 ubiquitin ligase, thereby interfering with the association between TRIM25 and retinoic acid-inducible gene I (RIG-I) and inhibiting TRIM25-mediated RIG-I ubiquitination and activation. Type I IFN production induced by poly I·C or Sendai virus (SeV) was suppressed by the SARS-CoV N protein. SARS-CoV replication was increased by overexpression of the full-length N protein but not N amino acids 1 to 361, which could not interact with TRIM25. These findings provide an insightful interpretation of the SARS-CoV-mediated host innate immune suppression caused by the N protein.IMPORTANCE The SARS-CoV N protein is essential for the viral life cycle and plays a key role in the virus-host interaction. We demonstrated that the interaction between the C terminus of the N protein and the SPRY domain of TRIM25 inhibited TRIM25-mediated RIG-I ubiquitination, which resulted in the inhibition of IFN production. We also found that the Middle East respiratory syndrome CoV (MERS-CoV) N protein interacted with TRIM25 and inhibited RIG-I signaling. The outcomes of these findings indicate the function of the coronavirus N protein in modulating the host's initial innate immune response.

show abstract

Section: Discussionmentioning

confidence: 99%

The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination

Hu¹,

Li²,

Gao³

et al. 2017

J Virol

272

315

View full text Add to dashboard Cite

show abstract

“…TRIM25 has been shown to play other functions in innate immunity. It was shown to positively regulate Melanoma Differentiation‐Associated gene 5 (MDA5)‐mediated signaling through tumor Necrosis factor receptor‐associated factor 6 (TRAF6), an E3 ubiquitin protein ligase, leading to activation of NF‐κB (Lee, Kim, Choi, Yi, & Inn, ). TRIM25 has also been shown to enhance the activity of zinc‐finger antiviral protein (ZAP), which is a known antiviral protein, this interaction will be addressed later in this review (Li et al, ; Zheng et al, ).…”

Section: Trim25's Role In Innate Immunitymentioning

confidence: 99%

TRIM25 and its emerging RNA‐binding roles in antiviral defense

2020

View full text Add to dashboard Cite

The innate immune system is the body's first line of defense against viruses, with pattern recognition receptors (PRRs) recognizing molecules unique to viruses and triggering the expression of interferons and other anti-viral cytokines, leading to the formation of an anti-viral state. The tripartite motif containing 25 (TRIM25) is an E3 ubiquitin ligase thought to be a key component in the activation of signaling by the PRR retinoic acid-inducible gene I protein (RIG-I). TRIM25 has recently been identified as an RNA-binding protein, raising the question of whether its RNA-binding activity is important for its role in innate immunity. Here, we review TRIM25's mechanisms and pathways in noninfected and infected cells. We also introduce models that explain how

show abstract

“…Furthermore, 14-3-3 proteins and TRIM25 serve as vital co-factors in the signaling of viral nucleic acid sensors, such as retinoic acid-inducible gene I (RIG-I) and MDA5 [78]. In this case, 14-3-3 proteins stabilize the interaction of TRIM25 with RIG-I, thus facilitating the ubiquitination of RIG-I [89].…”

Section: Role Of 14-3-3 In Dna Virusesmentioning

confidence: 99%

The Multifarious Role of 14-3-3 Family of Proteins in Viral Replication

Nathan

Lal

2020

Viruses

View full text Add to dashboard Cite

The 14-3-3 proteins are a family of ubiquitous and exclusively eukaryotic proteins with an astoundingly significant number of binding partners. Their binding alters the activity, stability, localization, and phosphorylation state of a target protein. The association of 14-3-3 proteins with the regulation of a wide range of general and specific signaling pathways suggests their crucial role in health and disease. Recent studies have linked 14-3-3 to several RNA and DNA viruses that may contribute to the pathogenesis and progression of infections. Therefore, comprehensive knowledge of host–virus interactions is vital for understanding the viral life cycle and developing effective therapeutic strategies. Moreover, pharmaceutical research is already moving towards targeting host proteins in the control of virus pathogenesis. As such, targeting the right host protein to interrupt host–virus interactions could be an effective therapeutic strategy. In this review, we generated a 14-3-3 protein interactions roadmap in viruses, using the freely available Virusmentha network, an online virus–virus or virus–host interaction tool. Furthermore, we summarize the role of the 14-3-3 family in RNA and DNA viruses. The participation of 14-3-3 in viral infections underlines its significance as a key regulator for the expression of host and viral proteins.

show abstract

Regulation of MDA5-MAVS Antiviral Signaling Axis by TRIM25 through TRAF6-Mediated NF-κB Activation

Cited by 43 publications

References 23 publications

The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination

The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination

TRIM25 and its emerging RNA‐binding roles in antiviral defense

The Multifarious Role of 14-3-3 Family of Proteins in Viral Replication

Contact Info

Product

Resources

About