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.

  • Journal Club
  • Published:

Therapeutic strategies

Virus–host warfare by PROTACs

Nature Reviews Molecular Cell Biology volume 25, page 675 (2024)Cite this article

Subjects

Over the past 35 years, the scientific community has achieved tremendous strides towards uncovering the mechanistic basis for myriad diseases. An early example of such success is the discovery by Peter Howley’s laboratory at the National Cancer Institute in the 1990s, of how the human papilloma virus (HPV) oncoprotein E6 usurps the host ubiquitin E3 ligase E6AP (also known as UBE3A) to induce degradation of the tumour suppressor p53 (Scheffner et al., 1993). This landmark study revealed the enzymatic activities required for HPV-driven cervical cancer and paved the way for the development of proteolysis-targeting chimeras (PROTACs) as a therapeutic strategy (Tsai et al., 2024). In parallel, the laboratories of Doug Lowy and John Schiller discovered that the HPV capsid protein L1 could be used to develop a vaccine to prevent HPV-driven cancers (Kirnbauer et al., 1992).

The discovery of viral-induced degradation of a host protein by hijacking the ubiquitination machinery inspired new therapeutic strategies whereby small molecules are used to direct the ubiquitination machinery to disease-associated proteins to induce their degradation. Following the discovery of E6-driven degradation of p53, a patent application for the PROTAC approach was submitted in 1999, and molecular targeting by PROTACs now fuels a growing sector of biomedical technology.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

References

Original articles

  • Scheffner, M. et al. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 75, 495–505 (1993)

    Article  CAS  PubMed  Google Scholar 

  • Kirnbauer, R. et al. Papillomavirus L1 major capsid protein self-assembles into virus-like particles that are highly immunogenic. Proc. Natl Acad. Sci. USA 89, 12180–12184 (1992)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Related articles

Download references

Author information

Authors and Affiliations

  1. Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA

    Kylie J. Walters

Authors
  1. Kylie J. Walters
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kylie J. Walters.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Walters, K.J. Virus–host warfare by PROTACs. Nat Rev Mol Cell Biol 25, 675 (2024). https://doi.org/10.1038/s41580-024-00761-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41580-024-00761-9

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer