Highlights•E3 ligases recruit substrates for proteasomal degradation by recognition of
degrons.•Crystal structures reveal the structural basis and mechanism of degron …

Abstract PROteolysis TArgeting Chimeras (PROTACs) technology is a new protein-
degradation strategy that has emerged in recent years. It uses bifunctional small molecules …

Manipulation of the ubiquitin–proteasome system to achieve targeted degradation of
proteins within cells using chemical tools and drugs has the potential to transform …

Conspectus One of the biggest bottlenecks in modern drug discovery efforts is in tackling the
undruggable proteome. Currently, over 85% of the proteome is still considered undruggable …

Ligand-induced protein degradation has emerged as a compelling approach to promote the
targeted elimination of proteins from cells by directing these proteins to the ubiquitin …

E3 ubiquitin ligases are key enzymes within the ubiquitin proteasome system which catalyze
the ubiquitination of proteins, targeting them for proteasomal degradation. E3 ligases are …

PROteolysis TArgeting Chimeras (PROTACs) are of significant current interest for the
development of probe molecules and drug leads. However, they suffer from certain …

Controlled perturbation of protein activity is essential to study protein function in cells and
living organisms. Small molecules that hijack the cellular protein ubiquitination machinery to …

Targeted protein degradation (TPD) with proteolysis targeting chimeras (PROTACs),
heterobifunctional compounds consisting of protein targeting ligands linked to recruiters of …

Protein–protein interactions (PPIs) governing the recognition of substrates by E3 ubiquitin
ligases are critical to cellular function. There is significant therapeutic potential in the …