Mechanism of degrader-targeted protein ubiquitinability

• Published in: Science advances Vol. 10; no. 41; p. eado6492
• Main Authors: Crowe, Charlotte, Nakasone, Mark A, Chandler, Sarah, Craigon, Conner, Sathe, Gajanan, Tatham, Michael H, Makukhin, Nikolai, Hay, Ronald T, Ciulli, Alessio
• Format: Journal Article
• Language: English
• Published: United States 11.10.2024
• Subjects: Bromodomain Containing Proteins; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - metabolism; Cryoelectron Microscopy; Humans; Lysine - chemistry; Lysine - metabolism; Models, Molecular; Protein Binding; Proteolysis; Transcription Factors - chemistry; Transcription Factors - metabolism; Ubiquitin - metabolism; Ubiquitin-Conjugating Enzymes - chemistry; Ubiquitin-Conjugating Enzymes - metabolism; Ubiquitination; Von Hippel-Lindau Tumor Suppressor Protein - chemistry; Von Hippel-Lindau Tumor Suppressor Protein - metabolism

Small-molecule degraders of disease-driving proteins offer a clinically proven modality with enhanced therapeutic efficacy and potential to tackle previously undrugged targets. Stable and long-lived degrader-mediated ternary complexes drive fast and profound target degradation; however, the mechanis...