The Experts below are selected from a list of 1200 Experts worldwide ranked by ideXlab platform
Jiping Sheng - One of the best experts on this subject based on the ideXlab platform.
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molecular characterization and expression pattern of tripartite motif protein 39 in gallus gallus with a complete pry spry Domain
International Journal of Molecular Sciences, 2011Co-Authors: Chunqing Pan, Heng Zhao, Lin Shen, Jiping ShengAbstract:Members of tripartite motif (TRIM) proteins in mammals play important roles in multiple cellular processes in the immune system. In the present study we have obtained the chicken TRIM39 with the insertion of a base A at position 1006 bp, compared to the sequence in the NCBI database (Accession No: NM 001006196), which made TRIM39 fulfill the TRIM rule of Domain composition with both PRY, and SPRY Domains. The open reading frame consisted of 1392 bp encoding 463 amino acid residues. The amino acid sequences of TRIM39 protein in mammals were highly similar (from 91.48% to 99.61%), while chicken TRIM39 had relatively low homology with mammals (from 29.2% to 39.59%). Real time RT-PCR indicated that the mRNA expression level of TRIM39 was the highest in spleen, with a lower expression in liver, brain, and lung, suggesting it might be an important protein participating in the immune system.
Chunqing Pan - One of the best experts on this subject based on the ideXlab platform.
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molecular characterization and expression pattern of tripartite motif protein 39 in gallus gallus with a complete pry spry Domain
International Journal of Molecular Sciences, 2011Co-Authors: Chunqing Pan, Heng Zhao, Lin Shen, Jiping ShengAbstract:Members of tripartite motif (TRIM) proteins in mammals play important roles in multiple cellular processes in the immune system. In the present study we have obtained the chicken TRIM39 with the insertion of a base A at position 1006 bp, compared to the sequence in the NCBI database (Accession No: NM 001006196), which made TRIM39 fulfill the TRIM rule of Domain composition with both PRY, and SPRY Domains. The open reading frame consisted of 1392 bp encoding 463 amino acid residues. The amino acid sequences of TRIM39 protein in mammals were highly similar (from 91.48% to 99.61%), while chicken TRIM39 had relatively low homology with mammals (from 29.2% to 39.59%). Real time RT-PCR indicated that the mRNA expression level of TRIM39 was the highest in spleen, with a lower expression in liver, brain, and lung, suggesting it might be an important protein participating in the immune system.
Guangdi Li - One of the best experts on this subject based on the ideXlab platform.
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trim21 promotes innate immune response to rna viral infection through lys27 linked polyubiquitination of mavs
Journal of Virology, 2018Co-Authors: Huiyi Li, Rilin Deng, Yan Xu, Jingjing Wang, Guangdi LiAbstract:: Human innate immunity responds to viral infection by activating the production of interferons (IFNs) and proinflammatory cytokines. The mitochondrial adaptor molecule MAVS plays a critical role in innate immune response to viral infection. In this study, we show that TRIM21 (tripartite motif-containing protein 21) interacts with MAVS to positively regulate innate immunity. Under viral infection, TRIM21 is upregulated through the IFN/JAK/STAT signaling pathway. Knockdown of TRIM21 dramatically impairs innate immune response to viral infection. Moreover, TRIM21 interacts with MAVS and catalyzes its K27-linked polyubiquitination, thereby promoting the recruitment of TBK1 to MAVS. Specifically, the PRY-SPRY Domain of TRIM21 is the key Domain for its interaction with MAVS, while the RING Domain of TRIM21 facilitates the polyubiquitination chains of MAVS. In addition, the MAVS-mediated innate immune response is enhanced by both the PRY-SPRY and RING Domains of TRIM21. Mutation analyses of all the lysine residues of MAVS further revealed that Lys325 of MAVS is catalyzed by TRIM21 for the K27-linked polyubiquitination. Overall, this study reveals a novel mechanism by which TRIM21 promotes the K27-linked polyubiquitination of MAVS to positively regulate innate immune response, thereby inhibiting viral infection.IMPORTANCE Activation of innate immunity is essential for host cells to restrict the spread of invading viruses and other pathogens. MAVS plays a critical role in innate immune response to RNA viral infection. In this study, we demonstrated that TRIM21 targets MAVS to positively regulate innate immunity. Notably, TRIM21 targets and catalyzes K27-linked polyubiquitination of MAVS and then promotes the recruitment of TBK1 to MAVS, leading to upregulation of innate immunity. Our study outlines a novel mechanism by which the IFN signaling pathway blocks RNA virus to escape immune elimination.
Caroline A Jefferies - One of the best experts on this subject based on the ideXlab platform.
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Analysis of interaction Domains of IRF5 and TRIM21.
2014Co-Authors: Elisa Lazzari, Justyna Korczeniewska, Joan Ní Gabhann, Siobhán Smith, Betsy J. Barnes, Caroline A JefferiesAbstract:A, Exon schematic of IRF5 isoforms structure. DBD, DNA binding Domain; PEST, region rich in proline (P), glutamic acid (E), serine (S) and threonine (T) residues; IAD, IRF association Domain; SRR, Serine-Rich Region. Dotted lines represent deleted regions. The dark grey box in exon 6 represents the polymorphic 30 nucleotide insertion while *indicates the position of the alternative splicing site 48 nucleotides from exon 6 5′ end. B, Domain structure of TRIM21 (top) and GST-tagged PRY/SPRY Domain (bottom). C, Myc-IRF5 isoforms were overexpressed in HEK-293T and lysates were incubated with GST-PRY/SPRY TRIM21 (left panel) or GST alone (right panel) bound to glutathione agarose. Interaction of IRF5 isoforms was assessed by immunoblot (top panels) and total IRF5 expression in the whole cell lysate (WCL) is shown in the bottom panel. D, Schematic diagram of exons encoding full length IRF5-V3 (top) and exons deletions originating C-terminal (C1) or N-terminal (N1–N4) truncated proteins. E, Full length FLAG-IRF5 or deletion mutants were overexpressed in HEK-293T and lysates were incubated with GST-PRY/SPRY TRIM21 (top panel) or GST alone bound to glutathione agarose. Interaction of IRF5 was assessed by anti-FLAG immunoblot and total IRF5 expression in the whole cell lysate (WCL) is shown. Anti-GST immunoblots (bottom panels) show amount of GST-PRY/SPRY TRIM21 or GST incubated with cell lysates. *indicates non-specific signal. Band intensity was calculated and ratio between pulled-down signal and total expression in the whole cell lysate is shown (bottom graph).
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tyrosine phosphorylation of the e3 ubiquitin ligase trim21 positively regulates interaction with irf3 and hence trim21 activity
PLOS ONE, 2012Co-Authors: Kevin Stacey, Eamon P Breen, Caroline A JefferiesAbstract:Patients suffering from Systemic Lupus Erythematous (SLE) have elevated type I interferon (IFN) levels which correlate with disease activity and severity. TRIM21, an autoantigen associated with SLE, has been identified as an ubiquitin E3 ligase that targets the transcription factor IRF3 in order to turn off and limit type I IFN production following detection of viral and bacterial infection by Toll Like Receptors (TLRs). However, how the activity of TRIM21 is regulated downstream of TLRs is unknown. In this study we demonstrate that TRIM21 is tyrosine phosphorylated following TLR3 and TLR4 stimulation, suggesting that its activity is potentially regulated by tyrosine phosphorylation. Using Netphos, we have identified three key tyrosines that are strongly predicted to be phosphorylated, two of which are conserved between the human and murine forms of TRIM21, at residues 343, 388, and 393, all of which have been mutated from tyrosine to phenylalanine (Y343F, Y388F, and Y393F). We have observed that tyrosine phosphorylation of TRIM21 only occurs in the substrate binding PRY/SPRY Domain, and that Y393, and to a lesser extent, Y388 are required for TRIM21 to function as a negative regulator of IFN-β promoter activity. Further studies revealed that mutating Y393 to phenylalanine inhibits the ability of TRIM21 to interact with its substrate, IRF3, thus providing a molecular explanation for the lack of activity of Y393 on the IFN-β promoter. Our data demonstrates a novel role for tyrosine phosphorylation in regulating the activity of TRIM21 downstream of TLR3 and TLR4. Given the pathogenic role of TRIM21 in systemic autoimmunity, these findings have important implications for the development of novel therapeutics.
Heng Zhao - One of the best experts on this subject based on the ideXlab platform.
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molecular characterization and expression pattern of tripartite motif protein 39 in gallus gallus with a complete pry spry Domain
International Journal of Molecular Sciences, 2011Co-Authors: Chunqing Pan, Heng Zhao, Lin Shen, Jiping ShengAbstract:Members of tripartite motif (TRIM) proteins in mammals play important roles in multiple cellular processes in the immune system. In the present study we have obtained the chicken TRIM39 with the insertion of a base A at position 1006 bp, compared to the sequence in the NCBI database (Accession No: NM 001006196), which made TRIM39 fulfill the TRIM rule of Domain composition with both PRY, and SPRY Domains. The open reading frame consisted of 1392 bp encoding 463 amino acid residues. The amino acid sequences of TRIM39 protein in mammals were highly similar (from 91.48% to 99.61%), while chicken TRIM39 had relatively low homology with mammals (from 29.2% to 39.59%). Real time RT-PCR indicated that the mRNA expression level of TRIM39 was the highest in spleen, with a lower expression in liver, brain, and lung, suggesting it might be an important protein participating in the immune system.
