New class of molecule targets proteins outside cells for degradation

Whitworth, Claire; Ciulli, Alessio

doi:10.1038/d41586-020-02211-w

NEWS AND VIEWS
29 July 2020

New class of molecule targets proteins outside cells for degradation

Molecules have previously been made that induce protein destruction inside cells. A new class of molecule now induces the degradation of membrane and extracellular proteins — opening up avenues for drug discovery.

Claire Whitworth ⁰ &
Alessio Ciulli ¹

Claire Whitworth
1. Claire Whitworth is in the Division of Biological Chemistry and Drug Discovery, School of Life Sciences, James Black Centre, University of Dundee, Dundee DD1 5EH, UK.
View author publications

You can also search for this author in PubMed Google Scholar
Alessio Ciulli
1. Alessio Ciulli is in the Division of Biological Chemistry and Drug Discovery, School of Life Sciences, James Black Centre, University of Dundee, Dundee DD1 5EH, UK.
View author publications

You can also search for this author in PubMed Google Scholar

Access through your institution

Buy or subscribe

Most drugs act by binding to a specific site in a target protein to block or modulate the protein’s function. The activity of many proteins, however, cannot be altered in this way. An emerging class of drug instead brings proteins into proximity with other molecules, which then alter protein function in unconventional ways¹^–³. One such approach uses drug molecules called protein degraders, which promote the tagging of proteins with ubiquitin, another small protein. Tagged proteins are then broken down into small peptide molecules by the cell’s proteasome machinery. But because the ubiquitin-mediated degradation pathway occurs inside the cell, protein degraders developed so far attack mainly intracellular targets. Writing in Nature, Banik et al.⁴ now report a different mechanism that opens up extracellular and membrane-bound proteins for targeted degradation.

Access options

Access through your institution

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Nature 584, 193-194 (2020)

doi: https://doi.org/10.1038/d41586-020-02211-w

References

Maniaci, C. & Ciulli, A. Curr. Opin. Chem. Biol. 52, 145–156 (2019).
PubMed Article Google Scholar
Deshaies, R. J. Nature 580, 329–338 (2020).
PubMed Article Google Scholar
Gerry, C. J. & Schreiber, S. L. Nature Chem. Biol. 16, 369–378 (2020).
PubMed Article Google Scholar
Banik, S. M. et al. Nature 584, 291–297 (2020).
Article Google Scholar
Burslem, G. M. & Crews, C. M. Cell 181, 102–114 (2020).
PubMed Article Google Scholar
Bensimon, A. et al. Cell Chem. Biol. 27, 728–739 (2020).
PubMed Article Google Scholar
Zhang, L., Riley-Gillis, B., Vijay, P. & Shen, Y. Mol. Cancer Ther. 18, 1302–1311 (2019).
PubMed Article Google Scholar
Roy, M. J. et al. ACS Chem. Biol. 14, 361–368 (2019).
PubMed Article Google Scholar
Hanan, E. J. et al. J. Med. Chem. https://doi.org/10.1021/acs.jmedchem.0c00093 (2020).
Article Google Scholar
Mullard, A. Nature Rev. Drug Discov. 19, 435 (2020).
Article Google Scholar
Chiu, M. L. & Gilliland, G. L. Curr. Opin. Struct. Biol. 38, 163–173 (2016).
PubMed Article Google Scholar
Takahashi, D. et al. Mol. Cell 76, 797–810 (2019).
PubMed Article Google Scholar