Hui Qiu, Fang Huang, Han Xiao, Binlian Sun and Rongge Yang. TRIM22 Inhibits the TRAF6-stimulated NF-κB Pathway by Targeting TAB2 for Degradation[J]. Virologica Sinica, 2013, 28(4): 209-215. doi: 10.1007/s12250-013-3343-4
Citation: Hui Qiu, Fang Huang, Han Xiao, Binlian Sun, Rongge Yang. TRIM22 Inhibits the TRAF6-stimulated NF-κB Pathway by Targeting TAB2 for Degradation .VIROLOGICA SINICA, 2013, 28(4) : 209-215.  http://dx.doi.org/10.1007/s12250-013-3343-4

TRIM22 Inhibits the TRAF6-stimulated NF-κB Pathway by Targeting TAB2 for Degradation

cstr: 32224.14.s12250-013-3343-4
  • 通讯作者: Binlian Sun, sunbl@wh.iov.cn; Rongge Yang, ryang@wh.iov.cn
  • 收稿日期: 2013-05-19
    录用日期: 2013-05-27
    出版日期: 2013-06-27
  • 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.

TRIM22 Inhibits the TRAF6-stimulated NF-κB Pathway by Targeting TAB2 for Degradation

  • Corresponding author: Binlian Sun, sunbl@wh.iov.cn Rongge Yang, ryang@wh.iov.cn
  • Received Date: 19 May 2013
    Accepted Date: 27 May 2013
    Published Date: 27 June 2013
  • 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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    1. 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.
        doi: 10.1371/journal.ppat.1000007

    2. 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.

    3. 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.
        doi: 10.1038/383443a0

    4. 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.
        doi: 10.1128/JVI.02548-12

    5. 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.

    6. 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.
        doi: 10.1007/s00705-011-1097-6

    7. 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.
        doi: 10.1007/s12250-011-3184-y

    8. Hayden M S, and Ghosh S. 2008. Shared principles in NF-kappaB signaling. Cell, 132:344-362.
        doi: 10.1016/j.cell.2008.01.020

    9. 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.
        doi: 10.1016/j.bbrc.2013.02.012

    10. 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.
        doi: 10.1016/j.molcel.2004.08.008

    11. 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.
        doi: 10.1111/j.1365-2443.2005.00852.x

    12. 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.
        doi: 10.1215/15228517-2008-083

    13. McNab F W, Rajsbaum R, Stoye J P, and O'Garra A. 2011. Tripartite-motif proteins and innate immune regulation. 0Curr Opin Immunol, 23:46-56.
        doi: 10.1016/j.coi.2010.10.021

    14. 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.
        doi: 10.1089/jir.2006.0180

    15. 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.
        doi: 10.1016/j.leukres.2006.12.012

    16. 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.
        doi: 10.1038/nri2413

    17. 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.
        doi: 10.1128/JVI.02072-08

    18. 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.
        doi: 10.1038/ni1577

    19. 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.

    20. 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.
        doi: 10.1074/jbc.M701913200

    21. 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.
        doi: 10.1074/jbc.270.25.14891

    22. 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.
        doi: 10.1038/35085597

    23. 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.
        doi: 10.1016/j.molimm.2012.02.118

    24. 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.
        doi: 10.1016/j.bbrc.2011.05.124

    25. 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.
        doi: 10.4049/jimmunol.176.2.1072

    26. 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.
        doi: 10.1038/cr.2013.21

    27. 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.
        doi: 10.4049/jimmunol.0903748

    28. 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.
        doi: 10.1371/journal.pone.0041255

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    TRIM22 Inhibits the TRAF6-stimulated NF-κB Pathway by Targeting TAB2 for Degradation

      Corresponding author: Binlian Sun, sunbl@wh.iov.cn
      Corresponding author: Rongge Yang, ryang@wh.iov.cn
    • Research Group of HIV Molecular Epidemiology and Virology, Center for Emerging Infectious Diseases, The State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China

    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.