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.

  • Original Article
  • Published:

p53 negatively regulates the expression of FAT10, a gene upregulated in various cancers

Oncogene volume 25, pages 2318–2327 (2006)Cite this article

Abstract

FAT10 is a member of the ubiquitin-like modifier family of proteins and has been implicated to play important roles in antigen presentation, cytokine response, apoptosis and mitosis. We have recently demonstrated the upregulation of FAT10 gene expression in 90% of hepatocellular carcinoma patients. Here, we identified and characterized the promoter of the FAT10 gene to elucidate the mechanism of FAT10 gene expression. Notably, we found that the 5′ untranslated region (5′UTR), from the transcription start site to 15 bases before the translational start site, displays significant promoter activity. Regions upstream of the 5′UTR (from +26 to −1997) do not confer any promoter activity. Curiously, FAT10 promoter activity and expression is significantly repressed in KB3-1 and HepG2 cells, which have wild-type p53, than in p53-negative Hep3B cells. The role of p53 in regulating FAT10 expression was evident by the significant downregulation (P<0.05) of FAT10 mRNA expression and promoter activity when wild-type p53 was transfected into p53-null Hep3B cells. Conversely, inhibiting p53 expression through siRNA against p53 significantly enhanced FAT10 expression and promoter activity. p53 was found to bind in vivo to the 5′ half consensus sequence of p53-binding site located at the FAT10 promoter. Hence, we propose that FAT10 is a downstream target of p53 and dysregulation of FAT10 expression in p53-defective cells could contribute to carcinogenesis.

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

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  • Aguiar J, Santurlidis S, Nowok J, Alexander C, Rudnicki D, Gispert S et al. (1999). Biochem Biophys Res Commun 254: 315–318.

  • Bates EE, Ravel O, Dieu MC, Ho S, Guret C, Bridon JM et al. (1997). Eur J Immunol 27: 2471–2477.

  • Boehm U, Klamp T, Groot M, Howard JC . (1997). Annu Rev Immunol 15: 749–795.

  • Bressac B, Galvin KM, Liang TJ, Isselbacher KJ, Wands JR, Ozturk M . (1990). Proc Natl Acad Sci USA 87: 1973–1977.

  • Brummelkamp TR, Bernards R, Agami R . (2002). Science 296: 550–553.

  • Chun AC, Jin DY . (2003). J Biol Chem 278: 37439–37450.

  • Clark IM, Rowan AD, Edwards DR, Bech-Hansen T, Mann DA, Bahr MJ et al. (1997). Biochem J 324 (Part 2): 611–617.

  • Dokmanovic M, Chang BD, Fang J, Roninson IB . (2002). Cancer Biol Ther 1: 24–27.

  • el-Deiry WS . (1998). Semin Cancer Biol 8: 345–357.

  • Fan W, Cai W, Parimoo S, Schwarz DC, Lennon GG, Weissman SM . (1996). Immunogenetics 44: 97–103.

  • Farmer G, Colgan J, Nakatani Y, Manley JL, Prives C . (1996). Mol Cell Biol 16: 4295–4304.

  • Haupt Y, Robles AI, Prives C, Rotter V . (2002). Oncogene 21: 8223–8231.

  • Hernando E, Nahle Z, Juan G, Diaz-Rodriguez E, Alaminos M, Hemann M et al. (2004). Nature 430: 797–802.

  • Ho J, Benchimol S . (2003). Cell Death Differ 10: 404–408.

  • Hoffman WH, Biade S, Zilfou JT, Chen J, Murphy M . (2002). J Biol Chem 277: 3247–3257.

  • Innocente SA, Abrahamson JL, Cogswell JP, Lee JM . (1999). Proc Natl Acad Sci USA 96: 2147–2152.

  • Jentsch S, Pyrowolakis G . (2000). Trends Cell Biol 10: 335–342.

  • Jesenberger V, Jentsch S . (2002). Nat Rev Mol Cell Biol 3: 112–121.

  • Kumanovics A, Takada T, Lindahl KF . (2003). Annu Rev Immunol 21: 629–657.

  • Lane DP . (1992). Nature 358: 15–16.

  • Lee CG, Ramachandra M, Jeang KT, Martin MA, Pastan I, Gottesman MM . (2000). FASEB J 14: 516–522.

  • Lee CG, Ren J, Cheong IS, Ban KH, Ooi LL, Yong Tan S et al. (2003). Oncogene 22: 2592–2603.

  • Lee KC, Crowe AJ, Barton MC . (1999). Mol Cell Biol 19: 1279–1288.

  • Levine AJ . (1997). Cell 88: 323–331.

  • Li GQ, Li H, Zhang HF . (2003). World J Gastroenterol 9: 1972–1975.

  • Liu YC, Pan J, Zhang C, Fan W, Collinge M, Bender JR et al. (1999). Proc Natl Acad Sci USA 96: 4313–4318.

  • Luo X, Tang Z, Rizo J, Yu H . (2002). Mol Cell 9: 59–71.

  • Maeda Y, Seidel SD, Wei G, Liu X, Sladek FM . (2002). Mol Endocrinol 16: 402–410.

  • Michel LS, Liberal V, Chatterjee A, Kirchwegger R, Pasche B, Gerald W et al. (2001). Nature 409: 355–359.

  • Moll UM, Riou G, Levine AJ . (1992). Proc Natl Acad Sci USA 89: 7262–7266.

  • Pagano M . (1997). FASEB J 11: 1067–1075.

  • Pines J . (1994). Nature 371: 742–743.

  • Raasi S, Schmidtke G, de Giuli R, Groettrup M . (1999). Eur J Immunol 29: 4030–4036.

  • Stahler F, Roemer K . (1998). Oncogene 17: 3507–3512.

  • Taylor WR, Schonthal AH, Galante J, Stark GR . (2001). J Biol Chem 276: 1998–2006.

  • Taylor WR, Stark GR . (2001). Oncogene 20: 1803–1815.

  • van den Elsen PJ, Gobin SJ, van Eggermond MC, Peijnenburg A . (1998). Immunogenetics 48: 208–221.

  • Vogelstein B, Lane D, Levine AJ . (2000). Nature 408: 307–310.

  • Vousden KH, Lu X . (2002). Nat Rev Cancer 2: 594–604.

  • Wang X, Jin DY, Ng RW, Feng H, Wong YC, Cheung AL et al. (2002). Cancer Res 62: 1662–1668.

  • Zhao R, Gish K, Murphy M, Yin Y, Notterman D, Hoffman WH et al. (2000). Genes Dev 14: 981–993.

Download references

Acknowledgements

This work was supported by grants from the Biomedical Research Council (BMRC), National Medical Research Council (NMRC), Singapore and the SingHealth Cluster Research Fund to Caroline GL Lee.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

    D W Zhang & C G L Lee

  2. Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    K-T Jeang

  3. Division of Medical Sciences, National Cancer Center, Singapore

    C G L Lee

Authors
  1. D W Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K-T Jeang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C G L Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C G L Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, D., Jeang, KT. & Lee, C. p53 negatively regulates the expression of FAT10, a gene upregulated in various cancers. Oncogene 25, 2318–2327 (2006). https://doi.org/10.1038/sj.onc.1209220

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209220

Keywords

This article is cited by

Search

Advanced search

Quick links