TARGETED PROTEIN DEGRADATION

Stick it to E3s

The limited availability of small-molecule ligands for E3 ubiquitin ligases stymies the development of next-generation degraders. Two recent papers report the identification of novel, covalent and PROTAC-compatible ligands that hijack the previously untargeted ligases RNF114 and DCAF16.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Out of around 600 E3 ligases, only a small subset is amenable for targeted protein degradation.

References

  1. 1.

    Sakamoto, K. M. et al. Proc. Natl. Acad. Sci. USA 98, 8554–8559 (2001).

    CAS  Article  Google Scholar 

  2. 2.

    Paiva, S. L. & Crews, C. M. Curr. Opin. Chem. Biol. 50, 111–119 (2019).

    CAS  Article  Google Scholar 

  3. 3.

    Buckley, D. L. et al. J. Am. Chem. Soc. 134, 4465–4468 (2012).

    CAS  Article  Google Scholar 

  4. 4.

    Vassilev, L. T. et al. Science 303, 844–848 (2004).

    CAS  Article  Google Scholar 

  5. 5.

    Ito, T. et al. Science 327, 1345–1350 (2010).

    CAS  Article  Google Scholar 

  6. 6.

    Winter, G. E. et al. Science 348, 1376–1381 (2015).

    CAS  Article  Google Scholar 

  7. 7.

    Lu, J. et al. Chem. Biol. 22, 755–763 (2015).

    CAS  Article  Google Scholar 

  8. 8.

    Winter, G. E. et al. Mol. Cell 67, 5–18.e19 (2017).

    CAS  Article  Google Scholar 

  9. 9.

    Spradlin, J. N. et al. Nat. Chem. Biol. https://doi.org/10.1038/s41589-019-0304-8 (2019).

  10. 10.

    Zhang, X. et al. Nat. Chem. Biol. https://doi.org/10.1038/s41589-019-0279-5 (2019).

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Georg E. Winter.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Brand, M., Winter, G.E. Stick it to E3s. Nat Chem Biol 15, 655–656 (2019). https://doi.org/10.1038/s41589-019-0312-8

Download citation

Further reading

Search

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