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.

  • News & Views
  • Published:

Probing the proteasome pathway

Nature Biotechnology volume 18, pages 494–496 (2000)Cite this article

The degradation of intracellular proteins is a complex process involving in eukaryotes a very large proteolytic complex—the 26S proteasome—and a multistep pathway involving the cofactor ubiquitin that provides exquisite selectivity and precise regulation. In recent years, major advances have been made in our understanding of this process and its biological importance, and efforts to exploit this knowledge for drug development are progressing rapidly. In this issue, Dantuma and colleagues1 describe a promising experimental method for following degradation of proteins in cells, which may prove useful in the search for novel inhibitors.

Few areas of biochemistry have been mined as successfully for industrial and medical applications as knowledge about proteolytic enzymes. Among the earliest biotechnology products were microbial and plant proteases for use in detergents or as meat tenderizers, and one of the most important achievements of the recombinant DNA industry was the production of tissue plasminogen activator, which has revolutionized the treatment of myocardial infarcts.

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: Protein breakdown by the ubiquitin (Ub)-proteasome pathway.

References

  1. Dantuma, N.P., Lindsten, K., Glas, R., Jellne, M., Masucci, M.G. Nat. Biotechnol. 18, 538– 543 (2000).

    Article  CAS  Google Scholar 

  2. Hershko, A. & Ciechanover, A. Annu. Rev. Biochem. 67, 425–479 (1998).

    Article  CAS  Google Scholar 

  3. Laney, J.D. & Hochstrasser, M. Cell 97, 427–430 (1999).

    Article  CAS  Google Scholar 

  4. Schwartz, A.L. & Ciechanover, A. Annu. Rev. Med. 50, 57–74 (1999).

    Article  CAS  Google Scholar 

  5. Baumeister, W., Walz, J., Zuhl, F. & Seemuller, E. Cell. 92, 367–380 (1998)

    Article  CAS  Google Scholar 

  6. Varshavsky, A. Proc. Natl. Acad. Sci. USA 93 12142– 12149 (1996).

    Article  CAS  Google Scholar 

  7. Kisselev, A.F., Akopian, T.N., Castillo, V. & Goldberg, A.L. Mol. Cell 4, 395–402 ( 1999).

    Article  CAS  Google Scholar 

  8. Etlinger, J.D. & Goldberg, A.L. Proc. Natl. Acad. Sci. USA 74, 54–58 (1977).

    Article  CAS  Google Scholar 

  9. Horwich, A.L., Weber-Ban, E.U. & Finley, D. Proc. Natl. Acad. Sci. USA 96 11033–11040 (1999).

    Article  CAS  Google Scholar 

  10. Lecker, S.H., Solomon, V., Mitch, W.E. & Goldberg, A.L. J. Nutr. 129, 227S–237S (1999).

    Article  CAS  Google Scholar 

  11. Lee, D.H. & Goldberg, A.L. Trends Cell Biol. 8, 397–403 (1998).

    Article  CAS  Google Scholar 

  12. Rock, K.L. & Goldberg, A.L. Annu. Rev. Immunol. 17, 739–779 (1999).

    Article  CAS  Google Scholar 

  13. Meng, L. et al. Proc. Natl. Acad. Sci. USA 96 10403– 10408 (1999).

    Article  CAS  Google Scholar 

  14. Adams, J. et al. Cancer Res. 59, 2615–2622 (1999).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. department of cell biology, professor of cell biology, Harvard Medical School, Boston, 02115, MA

    Alfred L. Goldberg

Authors
  1. Alfred L. Goldberg
    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

Goldberg, A. Probing the proteasome pathway. Nat Biotechnol 18, 494–496 (2000). https://doi.org/10.1038/75349

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/75349

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