Advertisement

Molecular and Cellular Biochemistry

, Volume 462, Issue 1–2, pp 51–59 | Cite as

Up-regulation of interferon-stimulated gene 15 and its conjugation machinery, UbE1L and UbcH8 expression by tumor necrosis factor-α through p38 MAPK and JNK signaling pathways in human lung carcinoma

  • Wannee Lertsooksawat
  • Ariyaphong WongnoppavichEmail author
  • Kongthawat ChairatvitEmail author
Article
  • 145 Downloads

Abstract

Interferon-stimulated gene 15 (ISG15) is a member of the family of ubiquitin-like proteins. Similar to ubiquitin, conjugation of ISG15 to cellular proteins requires cascade reactions catalyzed by at least 2 enzymes, UbE1L and UbcH8. Expression of ISG15 and its conjugates is up-regulated in many cancer cells, yet the underlying mechanism of up-regulation is still unclear. In this study, we showed that TNF-α, similar to the response by IFN-β, could directly induce expression of ISG15 and its conjugation machinery, UbE1L and UbcH8, in human lung carcinoma, A549. The early response of their expression was effectively blocked by specific inhibitors of p38 MAPK (SB202190) and JNK (SP600125), but not by B18R, a soluble type-I IFN receptor. In addition, luciferase reporter assay together with serial deletions and site-directed mutagenesis identified a putative C/EBPβ binding element in the ISG15 promoter, which is necessary to the response by TNF-α. Taken together, expression of ISG15 and ISG15 conjugation machinery in cancer cells is directly up-regulated by TNF-α via p38 MAPK and JNK pathways through the activation of C/EBPβ binding element in the ISG15 promoter. This study provides a new insight toward understanding the molecular mechanism of ISG15 system and inflammatory response in cancer progression.

Keywords

Cancer Inflammation ISG15 TNF-α 

Notes

Acknowledgements

This research project is supported by Mahidol University and Faculty of Dentistry, Mahidol University, and Ph.D. Research Grant, Faculty of Dentistry, Mahidol University (Grant No. 2560).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11010_2019_3609_MOESM1_ESM.tif (92 kb)
Supplementary Fig. 1The chemical structures of SP600125, SB202190, U0126, wortmannin, and PDTC. (TIFF 91 kb)
11010_2019_3609_MOESM2_ESM.tif (124 kb)
Supplementary Fig. 2Segments of UbE1L (a) and UbcH8 (b) promoter sequences with the putative C/EBPβ binding elements (boxed), and the interferon stimulated response element (ISRE; underlined). (TIFF 123 kb)

References

  1. 1.
    Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867CrossRefGoogle Scholar
  2. 2.
    Grivennikov SI, Karin M (2011) Inflammatory cytokines in cancer: tumour necrosis factor and interleukin 6 take the stage. Ann Rheum Dis 70(Suppl 1):104–108CrossRefGoogle Scholar
  3. 3.
    Aggarwal BB (2003) Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 3:745–756CrossRefGoogle Scholar
  4. 4.
    Balkwill F (2009) Tumour necrosis factor and cancer. Nat Rev Cancer 9:361–371CrossRefGoogle Scholar
  5. 5.
    Chairatvit K, Wongnoppavich A, Choonate S (2012) Up-regulation of interferon-stimulated gene15 and its conjugates by tumor necrosis factor-alpha via type I interferon-dependent and -independent pathways. Mol Cell Biochem 368:195–201CrossRefGoogle Scholar
  6. 6.
    Kumar S, Yoshida Y, Noda M (1993) Cloning of a cDNA which encodes a novel ubiquitin-like protein. Biochem Biophys Res Commun 195:393–399CrossRefGoogle Scholar
  7. 7.
    Zhang D, Zhang DE (2011) Interferon-stimulated gene 15 and the protein ISGylation system. J Interferon Cytokine Res 31:119–130CrossRefGoogle Scholar
  8. 8.
    Gessani S, Belardelli F, Pecorelli A, Puddu P, Baglioni C (1989) Bacterial lipopolysaccharide and gamma interferon induce transcription of beta interferon mRNA and interferon secretion in murine macrophages. J Virol 63:2785–2789PubMedPubMedCentralGoogle Scholar
  9. 9.
    Li J, Peet GW, Balzarano D, Li X, Massa P, Barton RW, Marcu KB (2001) Novel NEMO/IkappaB kinase and NF-kappa B target genes at the pre-B to immature B cell transition. J Biol Chem 276:18579–18590CrossRefGoogle Scholar
  10. 10.
    Manthey CL, Wang SW, Kinney SD, Yao Z (1998) SB202190, a selective inhibitor of p38 mitogen-activated protein kinase, is a powerful regulator of LPS-induced mRNAs in monocytes. J Leukoc Biol 64:409–417CrossRefGoogle Scholar
  11. 11.
    Desai SD, Haas AL, Wood LM, Tsai YC, Pestka S, Rubin EH, Saleem A, Nur EKA, Liu LF (2006) Elevated expression of ISG15 in tumor cells interferes with the ubiquitin/26S proteasome pathway. Cancer Res 66:921–928CrossRefGoogle Scholar
  12. 12.
    Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408CrossRefGoogle Scholar
  13. 13.
    Jung V, Pestka SB, Pestka S (1993) Cloning of polymerase chain reaction-generated DNA containing terminal restriction endonuclease recognition sites. Methods Enzymol 218:357–362CrossRefGoogle Scholar
  14. 14.
    Zhang G, Lin RK, Kwon YT, Li YP (2013) Signaling mechanism of tumor cell-induced up-regulation of E3 ubiquitin ligase UBR2. FASEB J 27:2893–2901CrossRefGoogle Scholar
  15. 15.
    Loeb KR, Haas AL (1992) The interferon-inducible 15-kDa ubiquitin homolog conjugates to intracellular proteins. J Biol Chem 267:7806–7813PubMedGoogle Scholar
  16. 16.
    Bennett BL, Sasaki DT, Murray BW, O’Leary EC, Sakata ST, Xu W, Leisten JC, Motiwala A, Pierce S, Satoh Y, Bhagwat SS, Manning AM, Anderson DW (2001) SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci USA 98:13681–13686CrossRefGoogle Scholar
  17. 17.
    Nemeth ZH, Deitch EA, Szabo C, Hasko G (2003) Pyrrolidinedithiocarbamate inhibits NF-kappaB activation and IL-8 production in intestinal epithelial cells. Immunol Lett 85:41–46CrossRefGoogle Scholar
  18. 18.
    Wymann MP, Bulgarelli-Leva G, Zvelebil MJ, Pirola L, Vanhaesebroeck B, Waterfield MD, Panayotou G (1996) Wortmannin inactivates phosphoinositide 3-kinase by covalent modification of Lys-802, a residue involved in the phosphate transfer reaction. Mol Cell Biol 16:1722–1733CrossRefGoogle Scholar
  19. 19.
    Favata MF, Horiuchi KY, Manos EJ, Daulerio AJ, Stradley DA, Feeser WS, Van Dyk DE, Pitts WJ, Earl RA, Hobbs F, Copeland RA, Magolda RL, Scherle PA, Trzaskos JM (1998) Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J Biol Chem 273:18623–18632CrossRefGoogle Scholar
  20. 20.
    Messeguer X, Escudero R, Farre D, Nunez O, Martinez J, Alba MM (2002) PROMO: detection of known transcription regulatory elements using species-tailored searches. Bioinformatics 18:333–334CrossRefGoogle Scholar
  21. 21.
    Maranto J, Rappaport J, Datta PK (2011) Role of C/EBP-beta, p38 MAPK, and MKK6 in IL-1beta-mediated C3 gene regulation in astrocytes. J Cell Biochem 112:1168–1175CrossRefGoogle Scholar
  22. 22.
    Han HG, Moon HW, Jeon YJ (2018) ISG15 in cancer: beyond ubiquitin-like protein. Cancer Lett 438:52–62CrossRefGoogle Scholar
  23. 23.
    Li C, Wang J, Zhang H, Zhu M, Chen F, Hu Y, Liu H, Zhu H (2014) Interferon-stimulated gene 15 (ISG15) is a trigger for tumorigenesis and metastasis of hepatocellular carcinoma. Oncotarget 5:8429–8441PubMedPubMedCentralGoogle Scholar
  24. 24.
    Pouyfung P, Choonate S, Wongnoppavich A, Rongnoparut P, Chairatvit K (2019) Anti-proliferative effect of 8alpha-tigloyloxyhirsutinolide-13-O-acetate (8alphaTGH) isolated from Vernonia cinerea on oral squamous cell carcinoma through inhibition of STAT3 and STAT2 phosphorylation. Phytomedicine 52:238–246CrossRefGoogle Scholar
  25. 25.
    Aouadi M, Jager J, Laurent K, Gonzalez T, Cormont M, Binetruy B, Le Marchand-Brustel Y, Tanti JF, Bost F (2007) p38MAP Kinase activity is required for human primary adipocyte differentiation. FEBS Lett 581:5591–5596CrossRefGoogle Scholar
  26. 26.
    Engelman JA, Lisanti MP, Scherer PE (1998) Specific inhibitors of p38 mitogen-activated protein kinase block 3T3-L1 adipogenesis. J Biol Chem 273:32111–32120CrossRefGoogle Scholar
  27. 27.
    Ramji DP, Foka P (2002) CCAAT/enhancer-binding proteins: structure, function and regulation. Biochem J 365:561–575CrossRefGoogle Scholar
  28. 28.
    Chuang JY, Wang YT, Yeh SH, Liu YW, Chang WC, Hung JJ (2008) Phosphorylation by c-Jun NH2-terminal kinase 1 regulates the stability of transcription factor Sp1 during mitosis. Mol Biol Cell 19:1139–1151CrossRefGoogle Scholar
  29. 29.
    Studzinski GP, Wang X, Ji Y, Wang Q, Zhang Y, Kutner A, Harrison JS (2005) The rationale for deltanoids in therapy for myeloid leukemia: role of KSR-MAPK-C/EBP pathway. J Steroid Biochem Mol Biol 97:47–55CrossRefGoogle Scholar
  30. 30.
    Trivedi AK, Bararia D, Christopeit M, Peerzada AA, Singh SM, Kieser A, Hiddemann W, Behre HM, Behre G (2007) Proteomic identification of C/EBP-DBD multiprotein complex: JNK1 activates stem cell regulator C/EBPalpha by inhibiting its ubiquitination. Oncogene 26:1789–1801CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Oral Biology, Faculty of DentistryMahidol UniversityBangkokThailand
  2. 2.Department of Pharmacology, Faculty of DentistryMahidol UniversityBangkokThailand
  3. 3.Department of Biochemistry, Faculty of MedicineChiang Mai UniversityChiang MaiThailand

Personalised recommendations