Stimulation of DDX3 expression by ginsenoside Rg3 through the Akt/p53 pathway activates the innate immune response via TBK1/IKKε/IRF3 signalling

Current Medicinal Chemistry

Volumn 21, Issue 8, 2014, Pages 1050-1060

  Choi, Yeo Jin ^a   Kang, Li Jung ^a   Lee, Seong Gene ^a  

^a Chonnam National University   (South Korea)

Author keywords

Akt; DDX3 RNA helicase; Ginsenoside Rg3; Hepatitis B; HepG2.2.15 cells; Innate immunity; Interferon ; P53

Indexed keywords

BETA INTERFERON; DEAD BOX PROTEIN; DEAD BOX PROTEIN DDX3; GINSENOSIDE RG 3; HEPATITIS B SURFACE ANTIGEN; I KAPPA B KINASE EPSILON; INTERFERON REGULATORY FACTOR 3; PHOSPHOTRANSFERASE; PROTEIN KINASE B; PROTEIN MDM2; PROTEIN P53; TANK BINDING KINASE 1; UNCLASSIFIED DRUG;

ARTICLE; CELL NUCLEUS; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; DRUG MECHANISM; ENZYME INHIBITION; HUMAN; HUMAN CELL; INNATE IMMUNITY; LUCIFERASE ASSAY; PROMOTER REGION; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; TRANSACTIVATION; TRANSIENT TRANSFECTION; UPREGULATION;

DEAD-BOX RNA HELICASES; GINSENOSIDES; HEP G2 CELLS; HUMANS; I-KAPPA B KINASE; IMMUNITY, INNATE; INTERFERON REGULATORY FACTOR-3; INTERFERON-BETA; PANAX; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEIN P53; UP-REGULATION;

EID: 84896366435     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/09298673113206660306     Document Type: Article

References (38)

1. Linder, P. Dead-box proteins: a family affair-active and passive players in RNP-remodeling. Nucleic Acids Res., 2006, 34, 4168-4180.
2. Lorsch, J.R. RNA chaperones exist and DEAD box proteins get a life. Cell, 2002, 109, 797-800.
3. Luking, A.; Stahl, U.; Schmidt, U. The protein family of RNA helicases. Crit. Rev. Biochem. Mol. Biol., 1998, 33, 259-296.
4. Tanner, N.K.; Linder, P. DExD/H NRA helicases: from generic motors to specific dissociation functions. Mol. Cell, 2001, 8, 251-262.
5. Rosner, A.; Rinkevich, B. The DDX3 subfamily of the DEAD box helicases: divergent roles as unveiled by studying different organisms and in vitro assays. Curr. Med. Chem., 2007, 14, 2517-2525.
6. Akira, S.; Takeda, K. Toll-like receptor signaling. Nat. Rev. Immunol., 2004, 4, 499-511.
7. Takeuchi, O.; Akira, S. Innate immunity to virus infection. Immunol. Rev., 2009, 227, 75-86.
8. van der Molen, R.G.; Sprengers, D.; Binda, R.S.; de Jong, E.C.; Niesters, H.G.; Kusters, J.G.; Kwekkeboom, J.; Janssen, H.L. Functional impairment of myeloid and plasmacytoid dendritic cells of patients with chronic hepatitis B. Hepatology, 2004, 40, 738-746.
9. Wu, M.; Xu, Y.; Lin, S.; Zhang, X.; Xiang, L.; Yuan, Z. Hepatitis B virus polymerase inhibits the interferon-inducible MyD88 promoter by blocking nuclear translocation of Stat1. J. Gen. Virol., 2007, 88, 3260-3269.
10. Schröder, M.; Baran, M.; Bowie, A.G. Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKe-mediated IRF activation. EMBO J., 2008, 27, 2147-2157.
11. Soulat, D.; Bürckstümmer, T.; Westermayer, S.; Goncalves, A.; Bauch, A.; Stefanovic, A.; Hantschel, O.; Bennett, K.L.; Decker, T.; Superti-Furga, G. The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response. EMBO J., 2008, 27, 2135-2146.
12. Oshiumi, H.; Ikeda, M.; Matsumoto, M.; Watanabe, A.; Takeuchi, O.; Akira, S.; Kato, N.; Shimotohno, K.; Seya, T. Hepatitis C virus core protein abrogates the DDX3 function that enhances IPS-1- mediated IFN-beta induction. PLoS One., 2010, 5, e14258.
13. Oshiumi, H.; Sakai, K.; Matsumoto, M.; Seya, T. DEAD/H box 3 (DDX3) helicase binds the RIG-1 adaptor IPS-1 to up-regulate IFN-b inducing potential. Eur. J. Immunol., 2010, 40, 940-948.
14. Yu, S.; Chen, J.; Wu, M.; Chen, H.; Kato, N.; Yuan, Z. Hepatitis B virus polymerase inhibits RIG-I- and Toll-like receptor 3-mediated beta interferon induction in human hepatocytes through interference with interferon regulatory factor 3 activation and dampening of the interaction between TBK1/IKKe and DDX3. J. Gen. Virol., 2010, 91, 2080-2090.
15. Wang, H.; Ryu, W.S. Hepatitis B virus polymerase blocks pattern recognition receptor signaling via interaction with DDX3: implications for immune evasion. PLoS Pathog., 2010, 6, e1000986.
16. Wang, H.; Kim, S.; Ryu, W.S. DDX3 DEAD-box RNA helicase inhibits hepatitis B virus reverse transcription by incorporation into nucleocapsids. J. Virol., 2009, 83, 5815-5824.
17. Kang, L.; Choi, Y.; Lee, S. Suppressive effects of ginsenoside Rg3 on hepatitis B virus replication via stimulation of TRAF6/TAK1 degradation and inhibition of JNK/AP-1 signalling. Int.J. Biochem. Cell Biol. accepted. 2013
18. Choi, Y.; Lee, S. The DEAD-box RNA helicase DDX3 interacts with DDX5, co-localizes with it in the cytoplasm during the G2/M phase of the cycle, and affects its shuttling during mRNP export. J. Cell. Biochem., 2012, 113, 985-996.
19. Liu, H.; Naismith, J.H. An efficient one-step site-directed deletion, insertion, single and multiple-site plasmid mutagenesis protocol. BMC Biotechnol., 2008, 8, 91.
20. Bhakat, K.K.; Mitra, S. Regulation of the human O(6)- methylguanine-DNA methyltransferase gene by transcriptional coactivators cAMP response element-binding protein-binding activators cAMP response element-binding protein-binding protein and p300. J. Biol. Chem., 2000, 275, 34197-34204.
21. Arika, S.; Uematsu, S.; Takeuchi, O. Pathogen recognition and innate immunity. Cell, 2006, 124, 783-801.
22. Honda, K.; Taniguchi, T. IRFs: master regulators of signalling by toll-like receptors and cytosolic pattern-recognition receptors. Nat. Rev. Immunol., 2006, 6, 644-658.
23. Wu, D.W.; Liu, W.S.; Wang, J.; Chen, C.Y.; Cheng, Y.W.; Lee, H. Reduced p21(WAF1/CIP1) via alteration of p53-DDX3 pathway is associated with poor relapse-free survival in early-stage human papillomavirus- associated lung cancer. Clin. Cancer Res., 2011, 17, 1895-1905.
24. Hupp, T.R.; Lane, D.P. Allosteric activation of latent p53 tetramers. Curr. Biol., 1994, 4, 865-875.
25. Moll, U.M.; Petrenko, O. The MDM2-p53 interaction. Mol. Cancer Res., 2003, 1, 1001-1008.
26. Ogawara, Y.; Kishishita, S.; Obata, T.; Isazawa, Y.; Suzuki, T.; Tanaka, K.; Masuyama, N.; Gotoh, Y. Akt enhances Mdm2- mediated ubiquitination and degradation of p53. J. Biol. Chem., 2002, 277, 21843-21850.
27. Schröder, M. Human DEAD-box protein 3 has multiple functions in gene regulation and cell cycle control and is a prime target for viral manipulation. Biochem. Pharmacol., 2010, 79, 297-306.
28. Yedavalli, V.S.; Neuveut, C.; Chi, Y.H.; Kleiman, L.; Jeang, K.T. Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev- RRe export function. Cell, 2004, 119, 381-392.
29. Ariumi, Y.; Kuroki, M.; Abe, K.; Dansako, H.; Ikeda, M.; Wakita, T.; Kato, N. DDX3 DEAD-box RNA helicase is required for hepatitis C RNA replication. J. Virol., 2007, 81, 13922-13926.
30. Kobayashi, T.; Walsh, M.C.; Choi, Y. The role of TRAF6 in signal transduction and immune response. Microbes Infect., 2004, 6, 1333-1338.
31. Wu, H.; Arron, J.R. TRAF6, a molecular bridge spanning adaptive immunity, innate immunity and osteoimmunology. Bioassays, 2003, 25, 1096-1105.
32. Levine, A.J. p53, the cellular gatekeeper for growth and division. Cell, 1997, 88, 323-331.
33. Nag, S.A.; Qin, J.J.; Wang, W.; Wang, M.H.; Wang, H.; Zhang, R. Ginsenosides as anticancer agents: in vitro and in vivo activities, structure-activity relationships, and molecular mechanisms of action. Front. Pharmacol., 2012, 3, 25.
34. He, B.C.; Gao, J.L.; Luo, X.; Luo, J.; Shen, J.; Wang, L.; Zhou, Q.; Wang, Y.T.; Luu, H.H.; Haydon, R.C.; Wang, C.Z.; Du, W.; Yuan, C.S.; He, T.C.; Zhang, B.Q. Ginsenoside Rg3 inhibits colorectal tumor growth through the down-regulation of Wnt/?-catenin signaling. Int. J. Oncol., 2011, 38, 437-445.
35. Wang, C.Z.; Aung, H.H.; Ni, M.; Wu, J.A.; Tong, R.; Wicks, S.; He, T.C.; Yuan, C.S. 2007. Red American ginseng: ginsenoside constituents and antiproliferative activities of heat-processed Panax quinquefolius roots. Plant Med., 2007, 73, 669-674.
36. Wang, X.; Wang, Y.; Ren, Z.; Qian, C.; Li, Y.; Wang, Q.; Zhang, Y.; Zheng, L.; Jiang, J.; Yang, C.; Wang, D.; Zhang, Y.; Fan, J.; Wang, Y. Protective effects of 20(s)-protopanaxatriol on viral myocarditis infected by coxsackievirus B3. Pathobiology, 2012, 79, 285-289.
37. Chao, C.H.; Chen, C.M.; Cheng, P.L.; Shih, J.W.; Tsou, A.P.; Lee, Y.H. DDX3, a DEAD box RNA helicase with tumor growthsuppressive property and transcriptional regulation activity of the p21waf1/clp1 promoter, as a candidate tumor suppressor. Cancer Res., 2006, 66, 6579-6588.
38. Botlagunta, M.; Vesuna, F.; Mironchik, Y.; Raman, A.; Lisok, A.; Winnard, P. Jr.; Mukadam, S.; Van Diest, P.; Chen, J.H.; Farabaugh, P.; Patel, A.H.; Raman, V. Oncogenic role of DDX3 in breast cancer biogenesis. Oncogene, 2008, 27, 3912-3922.