Harnessing UBR5 for targeted protein degradation of key transcriptional regulators

Asad M Taherbhoy; Danette L Daniels

doi:10.1016/j.tips.2023.09.001

Harnessing UBR5 for targeted protein degradation of key transcriptional regulators

Trends Pharmacol Sci. 2023 Nov;44(11):758-761. doi: 10.1016/j.tips.2023.09.001. Epub 2023 Sep 26.

Authors

Asad M Taherbhoy¹, Danette L Daniels²

Affiliations

¹ Foghorn Therapeutics, 500 Technology Square Suite 700, Cambridge, MA 02139, USA.
² Foghorn Therapeutics, 500 Technology Square Suite 700, Cambridge, MA 02139, USA. Electronic address: [email protected].

PMID: 37770316
DOI: 10.1016/j.tips.2023.09.001

Abstract

Targeted protein degradation (TPD) has opened the door for drugging transcriptional regulators, yet the number of proteins targeted and E3 ligases utilized remain limited. Here, we highlight UBR5 and propose multiple strategies by which this E3 ligase could be modulated to drive degradation of key transcriptional targets implicated in disease.

Keywords: HECT E3 ligase; PROTACs; molecular glue; nuclear receptors; transcription factors; ubiquitination.