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.

  • Brief Communication
  • Published:

Gli regulation by the opposing activities of Fused and Suppressor of Fused

Nature Cell Biology volume 2, pages 310–312 (2000)Cite this article

Hedgehog (Hh) proteins are secreted factors that control cell proliferation and cell-fate specification1. Hh signalling is mediated in vertebrates by the Gli zinc-finger transcription factors (Gli1, Gli2 and Gli3) and in Drosophila by the Gli homologue Cubitus interruptus (Ci)2,3. However, the mechanisms that regulate Gli/Ci activity are not fully understood. Genetic studies in Drosophila have identified a putative serine-threonine kinase, Fused (Fu), and a new protein, Suppressor of Fused (Su(fu)), as modulators of Ci activity2. Here we show that a human homologue of Drosophila Fu, hFu, regulates the activity of Gli1 and Gli2 on several levels. hFu converts Gli2 from a weak to a strong transcriptional activator, antagonizes the repressive effect of the human Su(fu) homologue, hSu(fu), on Gli1 and Gli2, and promotes nuclear localization of Gli1 and Gli2.

To identify possible regulators of Gli proteins, we isolated complementary DNAs encoding hFu, which shares a significant level of homology with dFu in the kinase domain (55%), but only a limited amount of homology over the remaining 1,052 amino acids (see Supplementary Information ). The gene encoding hFu ( hFu) was mapped to chromosome 2q35, close to the PAX3 gene, which is implicated in the Klein–Waardenburg syndrome (data not shown). PAX3 is a target of Sonic hedgehog (Shh) and it has been suggested that additional loci in the 2q35 region may regulate the PAX3 locus, thereby influencing the Klein–Waardenburg phenotype4.

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: Expression profile of vertebrate Fu and regulation of Gli activity.
Figure 2: hFu interacts with hSu(fu) and Gli proteins and regulates nuclear localization of Gli.
Figure 3: hFu promotes nuclear localization of Gli1

References

  1. Hammerschmidt, M., Brook, A. & McMahon, A. P. Trends Genet 13, 14– 21 (1997).

    Article  CAS  Google Scholar 

  2. Murone, M., Rosenthal, A. & de Sauvage, F. J. Exp. Cell Res. 253, 25– 33 (1999).

    Article  CAS  Google Scholar 

  3. Kalderon, D. Curr. Biol 7, R759–762 ( 1997).

    Article  CAS  Google Scholar 

  4. Pasteris, N. G., Trask, B. J., Sheldon, S. & Gorski, J. L. Hum. Mol. Genet. 2, 953–959 (1993).

    Article  CAS  Google Scholar 

  5. Carpenter, D. et al. Proc. Natl Acad. Sci. USA 95, 13630 –13634 (1998).

    Article  CAS  Google Scholar 

  6. Stone, D. M. et al. J. Cell Sci. 112, 4437– 4448 (1999).

    CAS  PubMed  Google Scholar 

  7. Murone, M., Rosenthal, A. & de Sauvage, F. J. Curr. Biol. 9, 76– 84 (1999).

    Article  CAS  Google Scholar 

  8. Sun, X. et al. J. Biol. Chem. 274, 16871– 16875 (1999).

    Article  CAS  Google Scholar 

  9. Robbins, D. J., et al. Cell 90, 225–234 (1997).

    Article  CAS  Google Scholar 

  10. Hanks, S. K. & Quinn, A. M. Methods Enzymol. 200 , 38–62 (1991).

    Article  CAS  Google Scholar 

  11. Therond, P. et al. Genetics 142, 1181– 1198 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Kogerman, P. et al. Nature Cell Biol. 1, 312– 319 (1999).

    Article  CAS  Google Scholar 

  13. Sasaki, H., Nishizaki, Y., Hui, C., Nakafuku, M. & Kondoh, H. Development 126, 3915– 3924 (1999).

    CAS  PubMed  Google Scholar 

  14. Thomas, J. A. et al. J. Immunol. 163, 978– 984 (1999).

    CAS  PubMed  Google Scholar 

  15. Ohlmeyer, J. T. & Kalderon, D. Nature 396, 749–753 (1998).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank V. Dixit and his laboratory staff for various reagents and for advice, P. Polakis, M. Hynes and G. Keller for discussions, and J. Ligos for preparing the figures.

Correspondence and requests for materials should be addressed to F.d.S. The nucleotide sequence of hFu has been deposited at GenBank under accession number AF200815.

Supplementary Information is available on Nature Cell Biology’s World-Wide Web site (http://www.nature.com/ncb) or as paper copy from the London editorial office of Nature Cell Biology.

Author information

Author notes

  1. Maximilien Murone

    Present address: Swiss Institute for Experimental Cancer Research, Chemin des Boveresses 155, 1066, Epalinges, Switzerland

Authors and Affiliations

  1. Department of Molecular Oncology, Genentech Inc., One DNA Way, South San Francisco, 94080, California, USA

    Maximilien Murone, Shiuh-Ming Luoh & Frederic J. de Sauvage

  2. Department of Molecular Biology, Genentech Inc., One DNA Way, South San Francisco, 94080, California, USA

    Donna Stone, Austin Gurney, Mark Armanini, Christa Grey & Arnon Rosenthal

  3. Department of Pharmacokinetics and Metabolism, Genentech Inc., One DNA Way, South San Francisco, 94080, California, USA

    Wenlu Li

Authors
  1. Maximilien Murone
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shiuh-Ming Luoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Donna Stone
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wenlu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Austin Gurney
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mark Armanini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christa Grey
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Arnon Rosenthal
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Frederic J. de Sauvage
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Frederic J. de Sauvage.

Supplementary information

Figure 1

Alignment of the amino-acid sequences of human and Drosophila Fused. (PDF 24 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Murone, M., Luoh, SM., Stone, D. et al. Gli regulation by the opposing activities of Fused and Suppressor of Fused. Nat Cell Biol 2, 310–312 (2000). https://doi.org/10.1038/35010610

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/35010610

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing