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TRIM22 inhibits the TRAF6-stimulated NF-κB pathway by targeting TAB2 for degradation

Abstract

Tripartite motif containing 22 (TRIM22), a member of the TRIM/RBCC family, has been reported to activate the nuclear factor-kappa B (NF-κB) pathway in unstimulated macrophage cell lines, but the detailed mechanisms governing this activation remains unclear. We investigated this mechanism in HEK293T cells. We found that overexpression of TRIM22 could activate the NF-κB pathway and conversely, could inhibit the tumor necrosis factor receptor-associated factor 6 (TRAF6)-stimulated NF-κB pathway in HEK293T cells. Further experiments showed that TRIM22 could decrease the self-ubiquitination of TRAF6, and interact with and degrade transforming growth factor-β activated kinase 1 binding protein 2 (TAB2), and that these effects could be partially rescued by a TRIM22 RING domain deletion mutant. Collectively, our data indicate that overexpression of TRIM22 may negatively regulate the TRAF6-stimulated NF-κB pathway by interacting with and degrading TAB2.

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References

  • Barr S D, Smiley J R, and Bushman F D. 2008. The interferon response inhibits HIV particle production by induction of TRIM22. PLoS Pathog, 4: e1000007.

    PubMed  Article  Google Scholar 

  • Besse A, Lamothe B, Campos A D, Webster W K, Maddineni U, Lin S C, Wu H, and Darnay B G. 2007. TAK1-dependent signaling requires functional interaction with TAB2/TAB3. J Biol Chem, 282: 3918–3928.

    PubMed  Article  CAS  Google Scholar 

  • Cao Z, Xiong J, Takeuchi M, Kurama T, and Goeddel D V. 1996. TRAF6 is a signal transducer for interleukin-1. Nature, 383: 443–446.

    PubMed  Article  CAS  Google Scholar 

  • Di Pietro A, Kajaste-Rudnitski A, Oteiza A, Nicora L, Towers G J, Mechti N, and Vicenzi E. 2013. TRIM22 Inhibits Influenza A Virus Infection by Targeting the Viral Nucleoprotein for Degradation. J Virol, 87: 4523–4533.

    PubMed  Article  Google Scholar 

  • Gao B, Duan Z, Xu W, and Xiong S. 2009. Tripartite motif-containing 22 inhibits the activity of hepatitis B virus core promoter, which is dependent on nuclear-located RING domain. Hepatology, 50: 424–433.

    PubMed  Article  CAS  Google Scholar 

  • Gong J, Shen X H, Qiu H, Chen C, and Yang R G. 2011. Rhesus monkey TRIM5alpha represses HIV-1 LTR promoter activity by negatively regulating TAK1/TAB1/TAB2/TAB3-complex-mediated NF-kappaB activation. Arch Virol, 156: 1997–2006.

    PubMed  Article  CAS  Google Scholar 

  • Gong J, Shen X H, Chen C, Qiu H, and Yang R G. 2011. Down-regulation of HIV-1 infection by inhibition of the MAPK signaling pathway. Virol Sin, 26: 114–122.

    PubMed  Article  CAS  Google Scholar 

  • Hayden M S, and Ghosh S. 2008. Shared principles in NF-kappaB signaling. Cell, 132: 344–362.

    PubMed  Article  CAS  Google Scholar 

  • Huang F, Xiao H, Sun B L, and Yang R G. 2013. Characterization of TRIM62 as a RING finger E3 ubiquitin ligase and its subcellular localization. Biochem Biophys Res Commun, 432: 208–213.

    PubMed  Article  CAS  Google Scholar 

  • Kanayama A, Seth R B, Sun L, Ea C K, Hong M, Shaito A, Chiu Y H, Deng L, and Chen Z J. 2004. TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains. Mol Cell, 15: 535–548.

    PubMed  Article  CAS  Google Scholar 

  • Kishida S, Sanjo H, Akira S, Matsumoto K, and Ninomiya-Tsuji J. 2005. TAK1-binding protein 2 facilitates ubiquitination of TRAF6 and assembly of TRAF6 with IKK in the IL-1 signaling pathway. Genes Cells, 10: 447–454.

    PubMed  Article  CAS  Google Scholar 

  • Kuwayama K, Matsuzaki K, Mizobuchi Y, Mure H, Kitazato K T, Kageji T, Nakao M, and Nagahiro S. 2009. Promyelocytic leukemia protein induces apoptosis due to caspase-8 activation via the repression of NFkappaB activation in glioblastoma. Neuro Oncol, 11: 132–141.

    PubMed  Article  CAS  Google Scholar 

  • McNab F W, Rajsbaum R, Stoye J P, and O’Garra A. 2011. Tripartite-motif proteins and innate immune regulation. Curr Opin Immunol, 23: 46–56.

    PubMed  Article  CAS  Google Scholar 

  • Obad S, Olofsson T, Mechti N, Gullberg U, and Drott K. 2007. Regulation of the interferon-inducible p53 target gene TRIM22 (Staf50) in human T lymphocyte activation. J Interferon Cytokine Res, 27: 857–864.

    PubMed  Article  CAS  Google Scholar 

  • Obad S, Olofsson T, Mechti N, Gullberg U, and Drott K. 2007. Expression of the IFN-inducible p53-target gene TRIM22 is down-regulated during erythroid differentiation of human bone marrow. Leuk Res, 31: 995–1001.

    PubMed  Article  CAS  Google Scholar 

  • Ozato K, Shin D M, Chang T H, and Morse H C, 3rd. 2008. TRIM family proteins and their emerging roles in innate immunity. Nat Rev Immunol, 8: 849–860.

    PubMed  Article  CAS  Google Scholar 

  • Poole E, Groves I, MacDonald A, Pang Y, Alcami A, and Sinclair J. 2009. Identification of TRIM23 as a cofactor involved in the regulation of NF-kappaB by human cytomegalovirus. J Virol, 83: 3581–3590.

    PubMed  Article  CAS  Google Scholar 

  • Shi M, Deng W, Bi E, Mao K, Ji Y, Lin G, Wu X, Tao Z, Li Z, Cai X, Sun S, Xiang C, and Sun B. 2008. TRIM30 alpha negatively regulates TLR-mediated NF-kappa B activation by targeting TAB2 and TAB3 for degradation. Nat Immunol, 9: 369–377.

    PubMed  Article  CAS  Google Scholar 

  • Sivaramakrishnan G, Sun Y, Rajmohan R, and Lin V C. 2009. B30.2/SPRY domain in tripartite motif-containing 22 is essential for the formation of distinct nuclear bodies. FEBS Lett, 583: 2093–2099.

    PubMed  Article  CAS  Google Scholar 

  • Tian Y, Zhang Y, Zhong B, Wang Y Y, Diao F C, Wang R P, Zhang M, Chen D Y, Zhai Z H, and Shu H B. 2007. RBCK1 negatively regulates tumor necrosis factor- and interleukin-1-triggered NF-kappaB activation by targeting TAB2/3 for degradation. J Biol Chem, 282: 16776–16782.

    PubMed  Article  CAS  Google Scholar 

  • Tissot C, and Mechti N. 1995. Molecular cloning of a new interferon-induced factor that represses human immunodeficiency virus type 1 long terminal repeat expression. J Biol Chem, 270: 14891–14898.

    PubMed  Article  CAS  Google Scholar 

  • Wang C, Deng L, Hong M, Akkaraju G R, Inoue J, and Chen Z J. 2001. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature, 412: 346–351.

    PubMed  Article  CAS  Google Scholar 

  • Wimmer N, Huber B, Wege A K, Barabas N, Rohrl J, Pfeffer K, and Hehlgans T. 2012. Lymphotoxin-beta receptor activation on macrophages ameliorates acute DSS-induced intestinal inflammation in a TRIM30alpha-dependent manner. Mol Immunol, 51: 128–135.

    PubMed  Article  CAS  Google Scholar 

  • Yu S, Gao B, Duan Z, Xu W, and Xiong S. 2011. Identification of tripartite motif-containing 22 (TRIM22) as a novel NF-kappaB activator. Biochem Biophys Res Commun, 410: 247–251.

    PubMed  Article  CAS  Google Scholar 

  • Zha J, Han K J, Xu L G, He W, Zhou Q, Chen D, Zhai Z, and Shu H B. 2006. The Ret finger protein inhibits signaling mediated by the noncanonical and canonical IkappaB kinase family members. J Immunol, 176: 1072–1080.

    PubMed  CAS  Google Scholar 

  • Zhang X, Zhang J, Zhang L, van Dam H, and ten Dijke P. 2013. UBE2O negatively regulates TRAF6-mediated NF-kappaB activation by inhibiting TRAF6 polyubiquitination. Cell Res, 23: 366–377.

    PubMed  Article  CAS  Google Scholar 

  • Zhong B, Zhang Y, Tan B, Liu T T, Wang Y Y, and Shu H B. 2010. The E3 ubiquitin ligase RNF5 targets virus-induced signaling adaptor for ubiquitination and degradation. J Immunol, 184: 6249–6255.

    PubMed  Article  CAS  Google Scholar 

  • Zurek B, Schoultz I, Neerincx A, Napolitano L M, Birkner K, Bennek E, Sellge G, Lerm M, Meroni G, Soderholm J D, and Kufer T A. 2012. TRIM27 negatively regulates NOD2 by ubiquitination and proteasomal degradation. PLoS One, 7: e41255.

    PubMed  Article  CAS  Google Scholar 

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Correspondence to Binlian Sun or Rongge Yang.

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Qiu, H., Huang, F., Xiao, H. et al. TRIM22 inhibits the TRAF6-stimulated NF-κB pathway by targeting TAB2 for degradation. Virol. Sin. 28, 209–215 (2013). https://doi.org/10.1007/s12250-013-3343-4

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  • DOI: https://doi.org/10.1007/s12250-013-3343-4

Keywords

  • TRIM22
  • NF-κB pathway
  • TRAF6
  • TAB2