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.

  • Correspondence
  • Published:

Ubiquitin ligases as cancer genes

Nature Reviews Cancer volume 4, page 654 (2004)Cite this article

Sirs

After conducting a census of 291 proven human cancer genes and classifying them according to function, Futreal et al. observed that the most prevalent and most significantly over-represented domain encoded by these cancer genes is the protein kinase domain. Their study — which used the human proteome extracted from SwissProt/TrEMBL databases — reported that 27 out of 643 known protein kinases were represented in the census, whereas only 6.3 would be predicted to be included by chance1. However, we were surprised to find no mention of ubiquitylation-related genes in this census. Sun and Chen recently discussed the respective roles of the ubiquitylation and phosphorylation mechanisms in cell signalling2. Notably, they pointed to the apparently similar overall numbers of ubiquitylation- and phosphorylation-related enzymes encoded by the human genome and suggested that the regulatory functions of protein ubiquitylation could be as diverse as those of phosphorylation.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

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

References

  1. Futreal, P. A. et al. A census of human cancer genes. Nature Rev. Cancer 4, 177–183 (2004).

    Article  CAS  Google Scholar 

  2. Sun, L. & Chen, Z. J. The novel functions of ubiquitination in signaling. Curr. Opin. Cell Biol. 16, 339–340 (2004).

    Article  CAS  Google Scholar 

  3. Birney, E. et al. Ensembl 2004. Nucleic Acids Res. 32 (Database issue), D468–D470 (2004).

    Article  CAS  Google Scholar 

  4. Mulder, N. J. et al. The InterPro Database, 2003 brings increased coverage and new features. Nucleic Acids Res. 31, 315–318 (2003).

    Article  CAS  Google Scholar 

  5. Meetei, A. R. et al. A novel ubiquitin ligase is deficient in Fanconi anemia. Nature Genet. 35, 165–170 (2003).

    Article  CAS  Google Scholar 

  6. Meulmeester, E. et al. Critical role for a central part of Mdm2 in the ubiquitylation of p53. Mol. Cell. Biol. 23, 4929–4938 (2003).

    Article  CAS  Google Scholar 

  7. Ohta, T. & Fukuda, M. Ubiquitin and breast cancer. Oncogene 23, 2079–2088 (2004).

    Article  CAS  Google Scholar 

  8. Sanjay, A., Horne, W. C. & Baron, R. The Cbl family: ubiquitin ligases regulating signaling by tyrosine kinases. Sci. STKE 27 Nov 2001 (doi:10.1126/stke.2001.110.pe40).

    Article  CAS  Google Scholar 

  9. Kondo, K. & Kaelin, W. G. Jr. The von Hippel-Lindau tumor suppressor gene. Exp. Cell Res. 264, 117–125 (2001).

    Article  CAS  Google Scholar 

  10. Blagosklonny, M. V. Do VHL and HIF-1 mirror p53 and Mdm-2? Degradation-transactivation loops of oncoproteins and tumor suppressors. Oncogene 20, 395–398 (2001).

    Article  CAS  Google Scholar 

  11. Yu, X., Chini, C. C., He, M., Mer, G. & Chen, J. The BRCT domain is a phospho-protein binding domain. Science 302, 639–642 (2003).

    Article  CAS  Google Scholar 

  12. Toby, G. G., Gherraby, W., Coleman, T. R. & Golemis, E. A. A novel RING finger protein, human enhancer of invasion 10, alters mitotic progression through regulation of cyclin B levels. Mol. Cell. Biol. 23, 2109–2122 (2003).

    Article  CAS  Google Scholar 

  13. Brummelkamp, T. R., Nijman, S. M., Dirac, A. M. & Bernards, R. Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-κB. Nature 424, 797–801 (2003).

    Article  CAS  Google Scholar 

  14. Kovalenko, A. et al. The tumour suppressor CYLD negatively regulates NF-κB signalling by deubiquitination. Nature 424, 801–805 (2003).

    Article  CAS  Google Scholar 

  15. Trompouki, E. et al. CYLD is a deubiquitinating enzyme that negatively regulates NF-κB activation by TNFR family members. Nature 424, 793–796 (2003).

    Article  CAS  Google Scholar 

  16. Scheel, H. & Hofmann, K. No evidence for PHD fingers as ubiquitin ligases. Trends Cell Biol. 13, 285–287 (2003).

    Article  CAS  Google Scholar 

  17. Aravind, L., Iyer, L. M. & Koonin, E. V. Scores of RINGS but no PHDs in ubiquitin signaling. Cell Cycle 2, 123–126 (2003).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

M.D. is supported by the National Center of Competence in Research Molecular Oncology, a research programme of the Swiss National Science Foundation.

Author information

Authors and Affiliations

  1. Service of Medical Genetics, University Hospital (CHUV), University of Lausanne, Lausanne, CH-1011, Switzerland

    Jacques S. Beckmann & Fabienne Maurer

  2. Swiss Institute of Bioinformatics (SIB), Epalinges, CH-1066, Switzerland

    Mauro Delorenzi & Laurent Falquet

Authors
  1. Jacques S. Beckmann
    View author publications

    Search author on:PubMed Google Scholar

  2. Fabienne Maurer
    View author publications

    Search author on:PubMed Google Scholar

  3. Mauro Delorenzi
    View author publications

    Search author on:PubMed Google Scholar

  4. Laurent Falquet
    View author publications

    Search author on:PubMed Google Scholar

Related links

Related links

Online links

SwissProt/TrEMBL

ENSEMBL

CBL

VHL

BRCA1

HEI10

CYLD

Rights and permissions

Reprints and permissions

About this article

Cite this article

Beckmann, J., Maurer, F., Delorenzi, M. et al. Ubiquitin ligases as cancer genes. Nat Rev Cancer 4, 654 (2004). https://doi.org/10.1038/nrc1299-c1

Download citation

  • Issue date:

  • DOI: https://doi.org/10.1038/nrc1299-c1

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