Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Article
  • Published:

HDAC4 inhibits the transcriptional activation of mda-7/IL-24 induced by Sp1

Cellular & Molecular Immunology volume 7, pages 221–226 (2010)Cite this article

Abstract

Melanoma differentiation-associated gene/interleukin-24 (mda-7/IL-24) is a cytokine that can activate monocytes and T helper 2 cells. The expression of mda-7/IL-24 gradually fades with the progression of melanoma, and it is undetectable at the metastatic stage. Ectopic expression of mda-7/IL-24 selectively suppresses growth and induces apoptosis in cancer cells with little harm to normal cells. However, the transcriptional regulation of the mda-7/IL-24 gene has not been extensively studied. In this study, we show that the expression of mda-7/IL-24 was upregulated by the histone deacetylase (HDAC) inhibitors trichostatin A (TSA) and sodium butyrate (NaBu), whereas it was downregulated by HDAC4. We also found that the histone acetylation level and the binding of the transcriptional factor Sp1 to the mad-7 promoter were reduced upon HDAC4 treatment. Moreover, the HDAC inhibitor TSA induced histone hyperacetylation and stimulated Sp1 binding to the mda-7/IL-24 promoter, which in turn enhanced the expression of mda-7/IL-24. Therefore, we conclude that histone acetylation modification plays an important role in the regulation of mda-7/IL-24 and that the transcription factor Sp1 participates in this process.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Caudell EG, Mumm JB, Poindexter N, Ekmekcioglu S, Mhashilkar AM, Yang XH et al. The protein product of the tumor suppressor gene, melanoma differentiation-associated gene 7, exhibits immunostimulatory activity and is designated IL-24. J Immunol 2002; 168: 6041–6046.

    Article  CAS  Google Scholar 

  2. Chada S, Sutton RB, Ekmekcioglu S, Ellerhorst J, Mumm JB, Leitner WW et al. MDA-7/IL-24 is a unique cytokine – tumor suppressor in the IL-10 family. Int Immunopharmacol 2004; 4: 649–667.

    Article  CAS  Google Scholar 

  3. Kotenko SV . The family of IL-10-related cytokines and their receptors: related, but to what extent? Cytokine Growth Factor Rev 2002; 13: 223–240.

    Article  CAS  Google Scholar 

  4. Ekmekcioglu S, Ellerhorst J, Mhashilkar AM, Sahin AA, Read CM, Prieto VG et al. Down-regulated melanoma differentiation associated gene (mda-7/IL-24) expression in human melanomas. Int J Cancer 2001; 94: 54–59.

    Article  CAS  Google Scholar 

  5. Madireddi MT, Dent P, Fisher PB . Regulation of mda-7/IL-24 gene expression during human melanoma differentiation. Oncogene 2000; 19: 1362–1368.

    Article  CAS  Google Scholar 

  6. Lebedeva IV, Su ZZ, Chang Y, Kitada S, Reed JC, Fisher PB . The cancer growth suppressing gene mda-7/IL-24 induces apoptosis selectively in human melanoma cells. Oncogene 2002; 21: 708–718.

    Article  CAS  Google Scholar 

  7. Sauane M, Lebedeva IV, Su ZZ, Choo HT, Randolph A, Valerie K et al. Melanoma differentiation associated gene-7/interleukin-24 promotes tumor cell-specific apoptosis through both secretory and nonsecretory pathways. Cancer Res 2004; 64: 2988–2993.

    Article  CAS  Google Scholar 

  8. Mhashilkar AM, Schrock RD, Hindi M, Liao J, Sieger K, Kourouma F et al. Melanoma differentiation associated gene-7 (mda-7/IL-24): a novel anti-tumor gene for cancer gene therapy. Mol Med 2001; 7: 271–282.

    Article  CAS  Google Scholar 

  9. Sauane M, Gopalkrishnan RV, Sarkar D, Su ZZ, Lebedeva IV, Dent P et al. mda-7/IL-24: novel cancer growth suppressing and apoptosis inducing cytokine. Cytokine Growth Factor Rev 2003; 14: 35–51.

    Article  CAS  Google Scholar 

  10. Livak KJ and Schmittgen TD . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25: 402–408.

    Article  CAS  Google Scholar 

  11. Mottet D, Pirotte S, Lamour V, Hagedorn M, Javerzat S, Bikfalvi A et al. HDAC4 represses p21(WAF1/Cip1) expression in human cancer cells through a Sp1-dependent, p53-independent mechanism. Oncogene 2009; 28: 243–256.

    Article  CAS  Google Scholar 

  12. Madireddi MT, Dent P, Fisher PB . AP-1 and C/EBP transcription factors contribute to mda-7/IL-24 gene promoter activity during human melanoma differentiation. J Cell Physiol 2000; 185: 36–46.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No. 30671184) and the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT0519).

Author information

Author notes

  1. Dr J Lu, Institute of Genetics and Cytology, Northeast Normal University, 5268 Renmin Street, Changchun 130024, China. E-mail: luj809@nenu.edu.cn

Authors and Affiliations

  1. Institute of Genetics and Cytology, Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, China

    Lina Pan, Hong Pan, Hao Jiang, Juan Du, Xiuli Wang, Baiqu Huang & Jun Lu

  2. College of Chemistry and Life Science, Tianjin Key Laboratory of Cyto-Genetical and Molecular Regulation, Tianjin Normal University, Tianjin, China

    Lina Pan

Authors
  1. Lina Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hong Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hao Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Juan Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiuli Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Baiqu Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jun Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pan, L., Pan, H., Jiang, H. et al. HDAC4 inhibits the transcriptional activation of mda-7/IL-24 induced by Sp1. Cell Mol Immunol 7, 221–226 (2010). https://doi.org/10.1038/cmi.2010.12

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2010.12

Keywords

This article is cited by

Search

Advanced search

Quick links