Our understanding of the ubiquitin code has greatly evolved from conventional E1, E2 and
E3 enzymes that modify Lys residues on specific substrates with a single type of ubiquitin …

Targeted protein degradation (TPD) is an emerging therapeutic modality with the potential to
tackle disease-causing proteins that have historically been highly challenging to target with …

Mammalian development demands precision. Millions of molecules must be properly
located in temporal order, and their function regulated, to orchestrate important steps in cell …

Cullin-RING ubiquitin ligases (CRLs) are dynamic modular platforms that regulate myriad
biological processes through target-specific ubiquitylation. Our knowledge of this system …

The ubiquitin system has become synonymous with the modification of lysine residues.
However, the substrate scope and diversity of the conjugation machinery have been …

Small-molecule degraders of disease-driving proteins offer a clinically proven modality with
enhanced therapeutic efficacy and potential to tackle previously undrugged targets. Stable …

The N-degron pathway targets proteins that bear a destabilizing residue at the N terminus
for proteasome-dependent degradation. In yeast, Ubr1—a single-subunit E3 ligase—is …

Ubiquitin (Ub) chain formation by homologous to E6AP C-terminus (HECT)-family E3 ligases
regulates vast biology, yet the structural mechanisms remain unknown. We used chemistry …

Abstract The APOBEC3 (A3) proteins are host antiviral cellular proteins that hypermutate the
viral genome of diverse viral families. In retroviruses, this process requires A3 packaging …

Targeted protein degradation (TPD) is an emerging therapeutic strategy that would benefit
from new chemical entities with which to recruit a wider variety of ubiquitin E3 ligases to …