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Updated: Jan 18, 2026

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
Published on: May 10, 2022
E3 ubiquitin ligases in signaling, disease, and therapeutics
Pirouz Ebadi1, Caleb M Stratton1, Shaun K Olsen1
1Department of Biochemistry & Structural Biology, and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Abstract:
The ubiquitin-proteasome system (UPS) is a central regulator of protein turnover and signaling, with E3 ubiquitin ligases conferring substrate specificity and chain-type control. Recent advances have revealed new mechanistic classes of E3 ligases and expanded our understanding of their roles in disease, including cancer, neurodegeneration, and immune dysfunction. These insights have fueled the development of targeted protein degradation strategies that harness the UPS to eliminate disease-associated proteins. Approaches such as proteolysis-targeting chimeras (PROTACs), molecular glues, and antibody-based degraders are broadening the druggable proteome. Despite this progress, key challenges remain, including limited E3 ligase diversity, difficulties in degrader delivery, and resistance mechanisms. This review outlines recent advances in E3 ligase biology and therapeutic degradation, emphasizing opportunities to expand and refine UPS-targeted interventions.
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