N/C-degron pathways and inhibitor development for PROTAC applications

Biochim Biophys Acta Gene Regul Mech. 2024 Mar;1867(1):194952. doi: 10.1016/j.bbagrm.2023.194952. Epub 2023 May 30.

Abstract

Ubiquitination is a fascinating post-translational modification that has received continuous attention since its discovery. In this review, we first provide a concise overview of the E3 ubiquitin ligases, delving into classification, characteristics and mechanisms of ubiquitination. We then specifically examine the ubiquitination pathways mediated by the N/C-degrons, discussing their unique features and substrate recognition mechanisms. Finally, we offer insights into the current state of development pertaining to inhibitors that target the N/C-degron pathways, as well as the promising advances in the field of PROTAC (PROteolysis TArgeting Chimeras). Overall, this review offers a comprehensive understanding of the rapidly-evolving field of ubiquitin biology.

Keywords: Degron; E3 ubiquitin ligase; Proteolysis-targeting chimera (PROTAC); Ubiquitination.

Publication types

  • Review

MeSH terms

  • Degrons*
  • Proteolysis
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases* / genetics
  • Ubiquitination

Substances

  • Ubiquitin-Protein Ligases
  • Ubiquitin