Nuclear hormone receptors (NRs) are ligand-binding transcription factors that are widely
targeted therapeutically. Agonist binding triggers NR activation and subsequent degradation …

Stress response pathways detect and alleviate adverse conditions to safeguard cell and
tissue homeostasis, yet their prolonged activation induces apoptosis and disrupts …

Targeted protein degradation (TPD) has opened the door for drugging transcriptional
regulators, yet the number of proteins targeted and E3 ligases utilized remain limited. Here …

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 …

UBR5 is a nuclear E3 ligase that ubiquitinates a vast range of substrates for proteasomal
degradation. This HECT domain‐containing ubiquitin ligase has recently been identified as …

Highlights•Networks have been successfully applied in biology and medicine for several
decades.•Network methods play a key role in personalized and precision medicine.•Rapid …

While reactive oxygen species (ROS) have long been known to drive aging and
neurodegeneration, their persistent depletion below basal levels also disrupts organismal …

Lys ubiquitination is catalysed by E3 ubiquitin ligases and is central to the regulation of
protein stability and cell signalling in normal and disease states. There are gaps in our …

Ubiquitin ligases (E3s) are pivotal specificity determinants in the ubiquitin system by
selecting substrates and decorating them with distinct ubiquitin signals. However, structure …

Mammalian cells make the decision to divide at the G1-S transition in response to diverse
signals impinging on the retinoblastoma protein Rb, a cell cycle inhibitor and tumor …