The E3 Ubiquitin Ligase TBK1 Mediates the Degradation of Multiple Picornavirus VP3 Proteins by Phosphorylation and Ubiquitination

Li, Dan; Yang, Wei; Ren, Jingjing; Ru, Yi; Zhang, Keshan; Fu, Shaozu; Liu, Xiangtao; Zheng, Haixue

doi:10.1128/jvi.01438-19

Cited by 21 publications

(19 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To resolve such challenges [22], Maltose binding protein (MBP), glutathione s-transferase (GST), and small ubiquitin-like modifier (SUMO) are commonly used fusion markers [23]. For our study, the Sumo protein played an important role in obtaining large quantities of cytoplasmic expressed recombinant proteins [24].…”

Section: Discussionmentioning

confidence: 99%

Antigenicity and Immunogenicity Analysis of the E. coli Expressed FMDV Structural Proteins; VP1, VP0, VP3 of the South African Territories Type 2 Virus

Wubshet

Ding

et al. 2021

Viruses

View full text Add to dashboard Cite

An alternative vaccine design approach and diagnostic kits are highly required against the anticipated pandemicity caused by the South African Territories type 2 (SAT2) Foot and Mouth Disease Virus (FMDV). However, the distinct antigenicity and immunogenicity of VP1, VP0, and VP3 of FMDV serotype SAT2 are poorly understood. Similarly, the particular roles of the three structural proteins in novel vaccine design and development remain unexplained. We therefore constructed VP1, VP0, and VP3 encoding gene (SAT2:JX014256 strain) separately fused with His-SUMO (histidine-small ubiquitin-related modifier) inserted into pET-32a cassette to express the three recombinant proteins and separately evaluated their antigenicity and immunogenicity in mice. The fusion protein was successfully expressed and purified by the Ni-NTA resin chromatography. The level of serum antibody, spleen lymphocyte proliferation, and cytokines against the three distinct recombinant proteins were analyzed. Results showed that the anti-FMDV humoral response was triggered by these proteins, and the fusion proteins did enhance the splenocyte immune response in the separately immunized mice. We observed low variations among the three fusion proteins in terms of the antibody and cytokine production in mice. Hence, in this study, results demonstrated that the structural proteins of SAT2 FMDV could be used for the development of immunodiagnostic kits and subunit vaccine designs.

show abstract

Section: Discussionmentioning

confidence: 99%

Antigenicity and Immunogenicity Analysis of the E. coli Expressed FMDV Structural Proteins; VP1, VP0, VP3 of the South African Territories Type 2 Virus

Wubshet

Ding

et al. 2021

Viruses

View full text Add to dashboard Cite

show abstract

“…5A & B). One of the possible mechanisms is that when one phosphorylation site is mutated, other phosphorylation sites could get phosphorylated to compensate for the loss of phosphorylation at that site, and therefore the overall phosphorylation of the single mutant protein would remain similar as that of wild type protein [15,42]. Such possibility led us to create a quadruple mutant in which all four potential sites were simultaneously mutated to alanine.…”

Section: Discussionmentioning

confidence: 99%

Protein kinase C regulates organic anion transporter 1 through phosphorylating ubiquitin ligase Nedd4–2

Liu

Zhang

et al. 2021

BMC Mol and Cell Biol

View full text Add to dashboard Cite

Background Organic anion transporter 1 (OAT1) is a drug transporter expressed on the basolateral membrane of the proximal tubule cells in kidneys. It plays an essential role in the disposition of numerous clinical therapeutics, impacting their pharmacological and toxicological properties. The activation of protein kinase C (PKC) is shown to facilitate OAT1 internalization from cell surface to intracellular compartments and thereby reducing cell surface expression and transport activity of the transporter. The PKC-regulated OAT1 internalization occurs through ubiquitination, a process catalyzed by a E3 ubiquitin ligase, neural precursor cell expressed developmentally down-regulated 4–2 (Nedd4–2). Nedd4–2 directly interacts with OAT1 and affects ubiquitination, expression and stability of the transporter. However, whether Nedd4–2 is a direct substrate for PKC-induced phosphorylation is unknown. Results In this study, we investigated the role of Nedd4–2 phosphorylation in the PKC regulation of OAT1. The results showed that PKC activation enhanced the phosphorylation of Nedd4–2 and increased the OAT1 ubiquitination, which was accompanied by a decreased OAT1 cell surface expression and transport function. And the effects of PKC could be reversed by PKC-specific inhibitor staurosporine. We further discovered that the quadruple mutant (T197A/S221A/S354A/S420A) of Nedd4–2 partially blocked the effects of PKC on Nedd4–2 phosphorylation and on OAT1 transport activity. Conclusions Our investigation demonstrates that PKC regulates OAT1 likely through direct phosphorylation of Nedd4–2. And four phosphorylation sites (T197, S221, S354, and S420) of Nedd4–2 in combination play an important role in this regulatory process.

show abstract

“…VP1 and VP3 play important roles in inhibiting the production of host interferons to weaken the host antiviral response. On the other hand, VP2 is involved in the induction of autophagy ( Feng et al, 2018 ; Li et al, 2019b ; Liu et al, 2020 ).…”

Section: Fmdv Proteins Regulate Host Innate Immunitymentioning

confidence: 99%

“…Besides, FMDV VP0 protein interacts with Poly (rC) binding protein 2 (PCBP2) to degrade VISA via apoptotic pathway, thereby increasing FMDV replication ( Li et al, 2019c ). The latest study has found that the TANK-binding kinase 1 (TBK1) protein can interact with VP3 and degrade VP3 by its kinase and E3 ubiquitin ligase activity to resist FMDV infection ( Li et al, 2019b ). In addition, microRNA-1307 could enhance the host immune response by promoting VP3 degradation through the proteasome pathway in PK-15 cells to inhibit FMDV replication ( Qi et al, 2019 ).…”

Section: Fmdv Proteins Regulate Host Innate Immunitymentioning

confidence: 99%

Advances in Foot-and-Mouth Disease Virus Proteins Regulating Host Innate Immunity

Peng

Yang

et al. 2020

Front. Microbiol.

Self Cite

View full text Add to dashboard Cite

Foot-and-mouth disease (FMD) is a highly contagious disease that affects cloven-hoofed animals such as pigs, cattle, and sheep. The disease is caused by the foot-and-mouth disease virus (FMDV) which has a non-enveloped virion with icosahedral symmetry that encapsulates a positive-sense, single-stranded RNA genome of ∼8.4 kb. FMDV infection causes obvious immunosuppressive effects on the host. In recent years, studies on the immunosuppressive mechanism of FMDV have become a popular topic. In addition, studies have shown that many FMDV proteins are involved in the regulation of host innate immunity and have revealed mechanisms by which FMDV proteins mediate host innate immunity. In this review, advances in studies on the mechanisms of interaction between FMDV proteins and host innate immunity are summarized to provide a comprehensive understanding of FMDV pathogenesis and the theoretical basis for FMD prevention and control.

show abstract

The E3 Ubiquitin Ligase TBK1 Mediates the Degradation of Multiple Picornavirus VP3 Proteins by Phosphorylation and Ubiquitination

Cited by 21 publications

References 49 publications

Antigenicity and Immunogenicity Analysis of the E. coli Expressed FMDV Structural Proteins; VP1, VP0, VP3 of the South African Territories Type 2 Virus

Antigenicity and Immunogenicity Analysis of the E. coli Expressed FMDV Structural Proteins; VP1, VP0, VP3 of the South African Territories Type 2 Virus

Protein kinase C regulates organic anion transporter 1 through phosphorylating ubiquitin ligase Nedd4–2

Advances in Foot-and-Mouth Disease Virus Proteins Regulating Host Innate Immunity

Contact Info

Product

Resources

About