Advances in targeted degradation of endogenous proteins

Sascha Roth, Luke Fulcher, Gopal Sapkota (Lead / Corresponding author)

Research output: Contribution to journalReview articlepeer-review

14 Citations (Scopus)
404 Downloads (Pure)

Abstract

Protein silencing is often employed as a means to aid investigations in protein function and is increasingly desired as a therapeutic approach. Several types of protein silencing methodologies have been developed, including targeting the encoding genes, transcripts, the process of translation or the protein directly. Despite these advances, most silencing systems suffer from limitations. Silencing protein expression through genetic ablation, for example by CRISPR/Cas9 genome editing, is irreversible, time consuming and not always feasible. Similarly, RNA interference approaches warrant prolonged treatments, can lead to incomplete protein depletion and are often associated with off-target effects. Targeted proteolysis has the potential to overcome some of these limitations. The field of targeted proteolysis has witnessed the emergence of many methodologies aimed at targeting specific proteins for degradation in a spatio-temporal manner. In this review, we provide an appraisal of the different targeted proteolytic systems and discuss their applications in understanding protein function, as well as their potential in therapeutics.

Original languageEnglish
Pages (from-to)2761-2777
Number of pages17
JournalCellular and Molecular Life Sciences
Volume76
Issue number14
Early online date27 Apr 2019
DOIs
Publication statusE-pub ahead of print - 27 Apr 2019

Keywords

  • Affinity-directed protein missile
  • AiD
  • Auxin
  • CRBN
  • FKBP12
  • HALO
  • Monobody
  • Nanobody
  • PROTAC
  • Proteasome
  • Proteolysis targeting chimera
  • Thalidomide
  • Ubiquitin
  • VHL

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