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 …

Methods to direct the degradation of protein targets with proximity-inducing molecules that
coopt the cellular degradation machinery are advancing in leaps and bounds, and diverse …

Targeted protein degradation is a novel pharmacology established by drugs that recruit
target proteins to E3 ubiquitin ligases. Based on the structure of the degrader and the target …

PROteolysis TArgeting Chimeras (PROTACs) are hetero-bifunctional small molecules that
can simultaneously recruit target proteins and E3 ligases to form a ternary complex …

Abstract The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway plays an essential
role in glucose metabolism, promoting glycolysis and resisting gluconeogenesis. PI3K/AKT …

Targeted protein degradation by the ubiquitin–proteasome system represents a new
strategy to destroy pathogenic proteins in human diseases, including cancer and …

Most cullin-RING ubiquitin ligases (CRLs) form homologous assemblies between a
neddylated cullin-RING catalytic module and a variable substrate-binding receptor (for …

Abstract The p97/Cdc48 ATPase and its ubiquitin receptors Ufd1-Npl4 are essential to
unfold ubiquitylated proteins in many areas of eukaryotic cell biology. In yeast, Cdc48-Ufd1 …

All eukaryotes require intricate protein networks to translate developmental signals into
accurate cell fate decisions. Mutations that disturb interactions between network …

N-degron E3 ubiquitin ligases recognize specific residues at the N-termini of substrates.
Although molecular details of N-degron recognition are known for several E3 ligases, the …