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. 2013 Jun 26;28(4):209–215. doi: 10.1007/s12250-013-3343-4

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

Hui Qiu 1, Fang Huang 1, Han Xiao 1, Binlian Sun 1,✉, Rongge Yang 1,✉
PMCID: PMC8208411  PMID: 23818111

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.

Keywords: TRIM22, NF-κB pathway, TRAF6, TAB2

Contributor Information

Binlian Sun, Phone: +86-27-87198736, FAX: +86-27-87198736, Email: sunbl@wh.iov.cn.

Rongge Yang, Phone: +86-27-87198736, FAX: +86-27-87198736, Email: ryang@wh.iov.cn.

References

  1. Barr S D, Smiley J R, Bushman F D. The interferon response inhibits HIV particle production by induction of TRIM22. PLoS Pathog. 2008;4:e1000007. doi: 10.1371/journal.ppat.1000007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Besse A, Lamothe B, Campos A D, Webster W K, Maddineni U, Lin S C, Wu H, Darnay B G. TAK1-dependent signaling requires functional interaction with TAB2/TAB3. J Biol Chem. 2007;282:3918–3928. doi: 10.1074/jbc.M608867200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cao Z, Xiong J, Takeuchi M, Kurama T, Goeddel D V. TRAF6 is a signal transducer for interleukin-1. Nature. 1996;383:443–446. doi: 10.1038/383443a0. [DOI] [PubMed] [Google Scholar]
  4. Di Pietro A, Kajaste-Rudnitski A, Oteiza A, Nicora L, Towers G J, Mechti N, Vicenzi E. TRIM22 Inhibits Influenza A Virus Infection by Targeting the Viral Nucleoprotein for Degradation. J Virol. 2013;87:4523–4533. doi: 10.1128/JVI.02548-12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gao B, Duan Z, Xu W, Xiong S. Tripartite motif-containing 22 inhibits the activity of hepatitis B virus core promoter, which is dependent on nuclear-located RING domain. Hepatology. 2009;50:424–433. doi: 10.1002/hep.23011. [DOI] [PubMed] [Google Scholar]
  6. Gong J, Shen X H, Qiu H, Chen C, Yang R G. Rhesus monkey TRIM5alpha represses HIV-1 LTR promoter activity by negatively regulating TAK1/TAB1/TAB2/TAB3-complex-mediated NF-kappaB activation. Arch Virol. 2011;156:1997–2006. doi: 10.1007/s00705-011-1097-6. [DOI] [PubMed] [Google Scholar]
  7. Gong J, Shen X H, Chen C, Qiu H, Yang R G. Down-regulation of HIV-1 infection by inhibition of the MAPK signaling pathway. Virol Sin. 2011;26:114–122. doi: 10.1007/s12250-011-3184-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hayden M S, Ghosh S. Shared principles in NF-kappaB signaling. Cell. 2008;132:344–362. doi: 10.1016/j.cell.2008.01.020. [DOI] [PubMed] [Google Scholar]
  9. Huang F, Xiao H, Sun B L, Yang R G. Characterization of TRIM62 as a RING finger E3 ubiquitin ligase and its subcellular localization. Biochem Biophys Res Commun. 2013;432:208–213. doi: 10.1016/j.bbrc.2013.02.012. [DOI] [PubMed] [Google Scholar]
  10. Kanayama A, Seth R B, Sun L, Ea C K, Hong M, Shaito A, Chiu Y H, Deng L, Chen Z J. TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains. Mol Cell. 2004;15:535–548. doi: 10.1016/j.molcel.2004.08.008. [DOI] [PubMed] [Google Scholar]
  11. Kishida S, Sanjo H, Akira S, Matsumoto K, Ninomiya-Tsuji J. TAK1-binding protein 2 facilitates ubiquitination of TRAF6 and assembly of TRAF6 with IKK in the IL-1 signaling pathway. Genes Cells. 2005;10:447–454. doi: 10.1111/j.1365-2443.2005.00852.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kuwayama K, Matsuzaki K, Mizobuchi Y, Mure H, Kitazato K T, Kageji T, Nakao M, Nagahiro S. Promyelocytic leukemia protein induces apoptosis due to caspase-8 activation via the repression of NFkappaB activation in glioblastoma. Neuro Oncol. 2009;11:132–141. doi: 10.1215/15228517-2008-083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McNab F W, Rajsbaum R, Stoye J P, O’Garra A. Tripartite-motif proteins and innate immune regulation. Curr Opin Immunol. 2011;23:46–56. doi: 10.1016/j.coi.2010.10.021. [DOI] [PubMed] [Google Scholar]
  14. Obad S, Olofsson T, Mechti N, Gullberg U, Drott K. Regulation of the interferon-inducible p53 target gene TRIM22 (Staf50) in human T lymphocyte activation. J Interferon Cytokine Res. 2007;27:857–864. doi: 10.1089/jir.2006.0180. [DOI] [PubMed] [Google Scholar]
  15. Obad S, Olofsson T, Mechti N, Gullberg U, Drott K. Expression of the IFN-inducible p53-target gene TRIM22 is down-regulated during erythroid differentiation of human bone marrow. Leuk Res. 2007;31:995–1001. doi: 10.1016/j.leukres.2006.12.012. [DOI] [PubMed] [Google Scholar]
  16. Ozato K, Shin D M, Chang T H, Morse H C., 3rd TRIM family proteins and their emerging roles in innate immunity. Nat Rev Immunol. 2008;8:849–860. doi: 10.1038/nri2413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Poole E, Groves I, MacDonald A, Pang Y, Alcami A, Sinclair J. Identification of TRIM23 as a cofactor involved in the regulation of NF-kappaB by human cytomegalovirus. J Virol. 2009;83:3581–3590. doi: 10.1128/JVI.02072-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
  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, Sun B. TRIM30 alpha negatively regulates TLR-mediated NF-kappa B activation by targeting TAB2 and TAB3 for degradation. Nat Immunol. 2008;9:369–377. doi: 10.1038/ni1577. [DOI] [PubMed] [Google Scholar]
  19. Sivaramakrishnan G, Sun Y, Rajmohan R, Lin V C. B30.2/SPRY domain in tripartite motif-containing 22 is essential for the formation of distinct nuclear bodies. FEBS Lett. 2009;583:2093–2099. doi: 10.1016/j.febslet.2009.05.036. [DOI] [PubMed] [Google Scholar]
  20. Tian Y, Zhang Y, Zhong B, Wang Y Y, Diao F C, Wang R P, Zhang M, Chen D Y, Zhai Z H, Shu H B. RBCK1 negatively regulates tumor necrosis factor- and interleukin-1-triggered NF-kappaB activation by targeting TAB2/3 for degradation. J Biol Chem. 2007;282:16776–16782. doi: 10.1074/jbc.M701913200. [DOI] [PubMed] [Google Scholar]
  21. Tissot C, Mechti N. Molecular cloning of a new interferon-induced factor that represses human immunodeficiency virus type 1 long terminal repeat expression. J Biol Chem. 1995;270:14891–14898. doi: 10.1074/jbc.270.25.14891. [DOI] [PubMed] [Google Scholar]
  22. Wang C, Deng L, Hong M, Akkaraju G R, Inoue J, Chen Z J. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature. 2001;412:346–351. doi: 10.1038/35085597. [DOI] [PubMed] [Google Scholar]
  23. Wimmer N, Huber B, Wege A K, Barabas N, Rohrl J, Pfeffer K, Hehlgans T. Lymphotoxin-beta receptor activation on macrophages ameliorates acute DSS-induced intestinal inflammation in a TRIM30alpha-dependent manner. Mol Immunol. 2012;51:128–135. doi: 10.1016/j.molimm.2012.02.118. [DOI] [PubMed] [Google Scholar]
  24. Yu S, Gao B, Duan Z, Xu W, Xiong S. Identification of tripartite motif-containing 22 (TRIM22) as a novel NF-kappaB activator. Biochem Biophys Res Commun. 2011;410:247–251. doi: 10.1016/j.bbrc.2011.05.124. [DOI] [PubMed] [Google Scholar]
  25. Zha J, Han K J, Xu L G, He W, Zhou Q, Chen D, Zhai Z, Shu H B. The Ret finger protein inhibits signaling mediated by the noncanonical and canonical IkappaB kinase family members. J Immunol. 2006;176:1072–1080. doi: 10.4049/jimmunol.176.2.1072. [DOI] [PubMed] [Google Scholar]
  26. Zhang X, Zhang J, Zhang L, van Dam H, ten Dijke P. UBE2O negatively regulates TRAF6-mediated NF-kappaB activation by inhibiting TRAF6 polyubiquitination. Cell Res. 2013;23:366–377. doi: 10.1038/cr.2013.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zhong B, Zhang Y, Tan B, Liu T T, Wang Y Y, Shu H B. The E3 ubiquitin ligase RNF5 targets virus-induced signaling adaptor for ubiquitination and degradation. J Immunol. 2010;184:6249–6255. doi: 10.4049/jimmunol.0903748. [DOI] [PubMed] [Google Scholar]
  28. Zurek B, Schoultz I, Neerincx A, Napolitano L M, Birkner K, Bennek E, Sellge G, Lerm M, Meroni G, Soderholm J D, Kufer T A. TRIM27 negatively regulates NOD2 by ubiquitination and proteasomal degradation. PLoS One. 2012;7:e41255. doi: 10.1371/journal.pone.0041255. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Virologica Sinica are provided here courtesy of Wuhan Institute of Virology, Chinese Academy of Sciences

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