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:

The C/EBP homologous protein CHOP (GADD153) is an inhibitor of Wnt/TCF signals

Oncogene volume 25, pages 3397–3407 (2006)Cite this article

Abstract

CHOP (GADD153) is a protein of the C/EBP family of transcriptional regulators, which dimerizes with other C/EBP members and changes their DNA-binding and transactivation properties. It induces growth arrest and apoptosis after endoplasmatic reticulum stress or DNA damage. CHOP is also expressed during early embryogenesis and upregulated in tumour tissues with defective Wnt signals. We report here that CHOP functions as a specific inhibitor of Wnt/T-cell factor (TCF) signalling. CHOP inhibits TCF-dependent transcription in human embryonic and colon cancer cell lines. Injection of CHOP mRNA into early Xenopus laevis embryos suppresses dorsal organizer formation and inhibits secondary axis formation and TCF-dependent transcription in response to Wnt-8, Dishevelled, β-Catenin and TCF-VP16. In embryos and human cells, this inhibition depends on the N-terminal transactivation domain of CHOP, whereas the C-terminal dimerization domain is dispensable. CHOP binds to TCF factors, thereby preventing the binding of TCF to its DNA recognition site. Our findings demonstrate a novel function of CHOP as a Wnt repressor.

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
Figure 7

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  • Barone MV, Crozat A, Tabaee A, Philipson L, Ron D . (1994). Genes Dev 8: 453–464.

  • Clevers H . (2004). Cancer Cell 5: 5–6.

  • Conn KJ, Gao WW, Ullman MD, McKeon-O’Malley C, Eisenhauer PB, Fine RE et al. (2002). J Neurosci Res 68: 755–760.

  • Crozat A, Aman P, Mandahl N, Ron D . (1993). Nature 363: 640–644.

  • Eastman Q, Grosschedl R . (1999). Curr Opin Cell Biol 11: 233–240.

  • Fawcett TW, Eastman HB, Martindale JL, Holbrook NJ . (1996). J Biol Chem 271: 14285–14289.

  • Fleming JV, Fontanier N, Harries DN, Rees WD . (1997). Mol Reprod Dev 48: 310–316.

  • Fontanier-Razzaq NC, Hay SM, Rees WD . (1999). Mol Reprod Dev 54: 326–332.

  • Friedman AD . (1996). Cancer Res 56: 3250–3256.

  • Heasman J, Crawford A, Goldstone K, Garner-Hamrick P, Gumbiner B, McCrea P et al. (1994). Cell 79: 791–803.

  • Hecht A, Kemler R . (2000). EMBO Rep 1: 24–28.

  • Houston DW, Kofron M, Resnik E, Langland R, Destree O, Wylie C et al. (2002). Development 129: 4015–4025.

  • Huelsken J, Birchmeier W . (2001). Curr Opin Genet Dev 11: 547–553.

  • Jaiswal AS, Marlow BP, Gupta N, Narayan S . (2002). Oncogene 21: 8414–8427.

  • Kao KR, Elinson RP . (1988). Dev Biol 127: 64–77.

  • Kim CH, Oda T, Itoh M, Jiang D, Artinger KB, Chandrasekharappa SC et al. (2000). Nature 407: 913–916.

  • Kim DG, You KR, Liu MJ, Choi YK, Won YS . (2002). J Biol Chem 277: 38930–38938.

  • Krieg PA, Melton DA . (1984). Nucl Acids Res 12: 7057–7070.

  • Leckstrom-Himes J, Xanthopoulos KG . (1998). J Biol Chem 273: 28545–28548.

  • Logan CY, Nusse R . (2004). Annu Rev Cell Dev Biol 20: 781–810.

  • Maytin EV, Habener JF . (1998). J Invest Dermatol 110: 238–246.

  • Maytin EV, Ubeda M, Lin JC, Habener JF . (2001). Exp Cell Res 267: 193–204.

  • Meneghini MD, Ishitani T, Carter JC, Hisamoto N, Ninomiya-Tsuji J, Thorpe CJ et al. (1999). Nature 399: 793–797.

  • Moon RT, Bowerman B, Boutros M, Perrimon N . (2002). Science 296: 1644–1646.

  • Newport J, Kirschner M . (1982). Cell 3: 675–686.

  • Nieuwkoop PD, Faber J . (1967). Normal Table of Xenopus laevis (Daudin). North Holland Publ.: Amsterdam, Holland.

    Google Scholar 

  • Oyadomari S, Takeda K, Takiguchi M, Gotoh T, Matsumoto M, Wada I et al. (2001). Proc Natl Acad Sci USA 98: 10845–10850.

  • Peifer M, Polakis P . (2000). Science 287: 1606–1609.

  • Pereira RC, Delany AM, Canalis E . (2004). Endocrinology 145: 1952–1960.

  • Rabbitts TH, Forster A, Larson R, Nathan P . (1993). Nat Genet 4: 175–180.

  • Ramji DP, Foka P . (2002). Biochem J 365: 561–575.

  • Rask K, Thorn M, Ponten F, Kraaz W, Sundfeldt K, Hedin L et al. (2000). Int J Cancer 86: 337–343.

  • Ron D, Habener JF . (1992). Genes Dev 6: 439–453.

  • Ross SE, Hemati N, Longo KA, Bennett CN, Lucas PC, Erickson RL et al. (2000). Science 289: 950–953.

  • Scott DW, Loo G . (2004). Carciogenesis 25: 2155–2164.

  • Sokol SY . (1999). Curr Opin Genet Dev 9: 405–410.

  • Taipale J, Beachy PA . (2001). Nature 411: 349–354.

  • Talukder AH, Wang R, Kumar R . (2002). Oncogene 21: 4289–4300.

  • Tang QQ, Lane MD . (2000). Proc Natl Acad Sci USA 97: 12446–12450.

  • Ubeda M, Habener JF . (2003). J Biol Chem 278: 40514–40520.

  • Ubeda M, Vallejo M, Habener JF . (1999). Mol Cell Biol 19: 7589–7599.

  • Ubeda M, Wang XZ, Zinszner H, Wu I, Habener JF, Ron D . (1996). Mol Cell Biol 16: 1479–1489.

  • Vonica A, Weng W, Gumbiner BM, Venuti JM . (2000). Dev Biol 217: 230–243.

  • Wang XZ, Kuroda M, Sok J, Batchvarova N, Kimmel R, Chung P et al. (1998). EMBO J 17: 3619–3630.

  • Wang XZ, Lawson B, Brewer JW, Zinszner H, Sanjay A, Mi LJ et al. (1996). Mol Cell Biol 16: 4273–4280.

  • Zinszner H, Kuroda M, Wang X, Batchvarova N, Lightfoot RT, Remotti H et al. (1998). Genes Dev 12: 982–995.

Download references

Acknowledgements

We thank P Gerke, W Kuehn, M Koettgen, A Kramer-Zucker and B Schermer for helpful discussions and advice. We are grateful to D Clevers, F McCormick, SL McKnight, EV Maytin, D Miller, D Moore, R Mulligan, D Ron, B Seed, S Sokol, and RC Schwartz for providing plasmids and P Daniel and H Mühl for cell lines. This project was supported by grants from the DFG 305/2 to JG and the SFB 592 to GW.

Author information

Author notes

  1. M Horndasch and S Lienkamp: Both authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Division of Nephrology, University Hospital of Freiburg, Freiburg, Germany

    M Horndasch, S Lienkamp, A Schmitt, G Walz & J Gloy

  2. Department of Medicine, Division of Nephrology and Hypertension, UKM Münster, Münster, Germany

    E Springer & H Pavenstädt

Authors
  1. M Horndasch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S Lienkamp
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E Springer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A Schmitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H Pavenstädt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G Walz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J Gloy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J Gloy.

Additional information

Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Horndasch, M., Lienkamp, S., Springer, E. et al. The C/EBP homologous protein CHOP (GADD153) is an inhibitor of Wnt/TCF signals. Oncogene 25, 3397–3407 (2006). https://doi.org/10.1038/sj.onc.1209380

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209380

Keywords

This article is cited by

Search

Advanced search

Quick links