Parkin negatively regulates the antiviral signaling pathway by targeting TRAF3 for degradation

Di, Xin; Gu, Haiyan; Liu, Enping; Sun, Qing

doi:10.1074/jbc.ra117.001201

Cited by 20 publications

(22 citation statements)

References 43 publications

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“…The TRAF3 functions as an essential scaffold protein to coordinate the assembly of signaling complexes downstream of PRRs and their adaptor proteins to promote IRF3/7 phosphorylation . Novel candidates targeting TRAF3 has been reported to be able to modulate antiviral signaling pathway . Our findings showed that SRA directly associated with TRAF3 and TRAF3 is necessary for the suppressive function of SRA on regulating type I IFN responses to HBV infection.…”

Section: Discussionmentioning

confidence: 61%

“…Ubiquitination and deubiquitination serve as important post‐translational regulatory mechanisms in the modulation of virus‐induced IFN response . Studies have indicated a crucial role of TRAF3 ubiquitination in the virus‐triggered IFN induction . Ubiquitin molecules are attached to TRAF3 as either K48‐ or K63‐linked chains, relying on the context .…”

Section: Discussionmentioning

confidence: 99%

“…Until now, a few members of DUBs have been determined to dampen type I IFN antiviral response through cleaving K63‐linked ubiquitin chains on TRAF3 . Meanwhile, some components interfering the interaction between TRAF3 and DUBs were also identified, which thus resulted in the regulation of type I IFN signaling . It is of interest to discover new molecules either function as a DUB or cooperate with the present known DUBs in regulating antiviral immunity.…”

Section: Introductionmentioning

confidence: 99%

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Scavenger receptor A impairs interferon response to HBV infection by limiting TRAF3 ubiquitination through recruiting OTUB1

et al. 2019

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The battle between hepatitis B virus (HBV) infection and the host immune defense determines the outcome of the disease. Scavenger receptor A (SRA) is a phagocytic pattern recognition receptor involved in various cellular processes, including lipid metabolism, recognition, and clearance of pathogens or modified self‐molecules. Emerging evidence pointed out that SRA might act as an immunomodulator that contributes to innate immune defense against invading pathogens. Herein, we examined the role of SRA in the initiation of type I interferon (IFN) response to HBV infection and the virus clearance. Our results showed that SRA‐deficient (SRA−/−) mice were resistant to HBV infection developed by hydrodynamic injection of HBV replicon plasmid. We found lower levels of HBV DNA and viral protein expression in SRA−/− mice, which was associated with enhanced type I IFN production, compared with wild‐type controls. Besides, we performed gain and loss of function experiments and determined that SRA inhibits innate antiviral immune responses to HBV. SRA could interact directly with tumor necrosis factor receptor‐associated factor 3 (TRAF3) and inhibit its K63‐linked ubiquitination. Moreover, we provided evidence that SRA negatively regulates the stability of TRAF3 protein by promoting the recruitment of OTUB1 to TRAF3. Our findings indicate that SRA plays a crucial role in innate immune signaling by targeting TRAF3 for degradation and balancing the innate antiviral immunity.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Scavenger receptor A impairs interferon response to HBV infection by limiting TRAF3 ubiquitination through recruiting OTUB1

et al. 2019

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“…The protein encoded by TRAF3 is a member of the TNF receptor associated factor (TRAF) protein family that participates in the signal transduction of CD40, a TNFR family member important for the activation of the immune response and was found to be a critical component of the lymphotoxin-beta receptor (LTbetaR) signaling complex, which induces NF-kappaB activation and cell death initiated by LTbeta ligation [48,49]. The ndings suggest that Parkin plays a novel role in innate immune signaling by targeting TRAF3 for degradation and maintaining the balance of innate antiviral immunity [50]. A TRAF3-NIK axis differentially regulates viral DNA vs RNA pathways in innate immune signaling [51].…”

Section: Role Of Candidate Genesmentioning

confidence: 99%

Genome-Wide Association Studies for Immunoglobulins in Colostrum and Serum in Chinese Holstein

Shan

Liu³

et al. 2020

Preprint

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Abstract BackgroundImmunoglobulins (Igs) are important components of the innate immune system, and fight pathogens as a part of the first defense line. Newborn dairy calves get maternal antibodies from colostrum. Therefore, contents of immunoglobulins in colostrum and serum of cows are essential traits when estimating potential natural disease resistance of calves. In this study, a genome-wide association study (GWAS) was performed to identify candidate genes that are responsible for the observed genetic variation of immunoglobulins contents in colostrum and blood in Holstein cows.ResultsColostrum, blood and hair follicle samples were collected from the 620 Chinese Holstein cows within 24 hours after calving. The concentration of IgG, IgG1, IgG2, IgA and IgM in both colostrum and serum were detected via ELISA methods, respectively. Using GCTA software, GWASs were performed with 88,934 SNPs genotyped by using Illumina 50K (54,609 SNPs) and GeneSeek 150K (140,668 SNPs) chips in which 50K chip were imputed to 150K SNPs with BEAGLE 3.0.4 software. As a result, 20 and 5 SNPs were detected genome-wide significantly associated with contents of the IgG and IgM in colostrum and serum (P<3.16E–6). In addition, 57, 11 and 10 SNPs were suggestive significantly associated with IgG, IgA and IgM traits (P<6.32E–5). Next, a total of 1,083 functional genes were identified that included or adjacent to these significant SNPs with a distance less than 1 Mb. Functional enrichment analysis showed that these genes were involved in immune related pathways, such as immune response, Fc gamma R-mediated phagocytosis, negative regulation of immunoglobulin secretion, humoral immune response, Fc-epsilon receptor and NF-kappaB signaling pathways. By integrating analysis of the functional enrichment and the known QTL data, we identified 21 candidate genes associated with contents of immunoglobulins in colostrum and serum, including ABR, TIMM22, CRK, MYO1C, RILP, SERPINF2, AKT1, BCL11B, HHIPL1, DYNC1H1, HSP90AA1, TRAF3, KLC1, IL6, PYCARD, ITGAM, TGFB1I1, GUSB, CRCP, RABGEF1 and SBDS.ConclusionsIn this study, we identified 21 candidate genes associated with immunoglobulins level in colostrum and serum in dairy cattle. This founding demonstrated the possibility of increasing immunity through selective breeding and provided an important information for molecular breeding of dairy cattle.

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“…It can inhibit cell growth, colony formation and migration and resist to TNFα and cisplatin-induced cell death [51]. TRAF3 was also known to function as a resident nuclear protein to impact B cell metabolism and exert powerful restraint upon B cell survival and activation in human and mice [52,53]. KLC1 encodes kinesin-1 protein that is a member of the kinesin light chain family.…”

Section: Candidate Genesmentioning

confidence: 99%

Genome-Wide Association Studies for Immunoglobulin Concentrations in Colostrum and Serum in Chinese Holstein

Lin

Liu³

et al. 2020

Preprint

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BackgroundThe early death and health problems of calves caused substantial economic losses in dairy industry. As the immune system has not been fully developed in the neonates, transport of passive immune substance such as immunoglobulins (Ig) from mothers to newborn calves is essential in protecting neonates from infections in their early life. Therefore, concentrations of immunoglobulins in the colostrum and serum of dairy cows are critical traits when estimating potential disease resistance of its offspring. ResultsColostrum, blood and hair follicle samples were collected from the 620 Chinese Holstein cows within 24 hours after calving. The concentration of total IgG, IgG1, IgG2, IgA and IgM in both colostrum and serum were detected via ELISA methods. With GCTA software, genome-wide association studies (GWASs) were performed with 88,934 SNPs genotyped by using Illumina 50K (54,609 SNPs) and GeneSeek 150K (140,668 SNPs) chips in which 50K chip were imputed to 150K SNPs with BEAGLE. As a result, 20, 1 and 4 significant SNPs were detected associated with the concentrations of IgG2, IgA and IgM at genome-wide level (P < 3.16E–6); 11, 11, 35, 11 and 10 significant SNPs were identified associated with total IgG, IgG1, IgG2, IgA and IgM at suggestive level (P < 6.32E–5). Such SNPs were located in or proximate to (±1 Mb) 1,083 genes, which were functionally implicated in biological processes and pathways, such as immune response, negative regulation of immunoglobulin secretion, Fc-epsilon receptor and NF-kappaB signaling pathways. By combining the biological functions and the known QTL data for immune traits in bovine, 21 promising candidate functional genes were identified for immunoglobulins concentrations in colostrum and serum in dairy cattle, they were ABR, TIMM22, CRK, MYO1C, RILP, SERPINF2, AKT1, BCL11B, HHIPL1, DYNC1H1, HSP90AA1, TRAF3, KLC1, IL6, PYCARD, ITGAM, TGFB1I1, GUSB, CRCP, RABGEF1 and SBDS.ConclusionsIn this study, we identified 21 candidate genes related to concentrations of immunoglobulins in colostrum and serum in dairy cattle by performing GWASs. Our findings provide a groundwork for unraveling the key genes and causal mutations affecting immunoglobulins levels in colostrum and important information for genetic improvement of such traits in dairy cattle.

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Parkin negatively regulates the antiviral signaling pathway by targeting TRAF3 for degradation

Cited by 20 publications

References 43 publications

Scavenger receptor A impairs interferon response to HBV infection by limiting TRAF3 ubiquitination through recruiting OTUB1

Scavenger receptor A impairs interferon response to HBV infection by limiting TRAF3 ubiquitination through recruiting OTUB1

Genome-Wide Association Studies for Immunoglobulins in Colostrum and Serum in Chinese Holstein

Genome-Wide Association Studies for Immunoglobulin Concentrations in Colostrum and Serum in Chinese Holstein

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