Publications by authors named "B L Schulman"
Background And Objectives: Despite extensive efforts, the mechanisms underlying pain after axonal injury remain incompletely understood. Pain following corneal refractive surgery offers a valuable human model for investigating trigeminal axonal injury because laser-assisted in situ keratomileusis (LASIK) severs axons of trigeminal ganglion neurons innervating the cornea. While the majority of patients are pain-free shortly after surgery, a minority endure persistent postoperative ocular pain.
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- This study focuses on how E3 ligases interact with substrates through specific C-degron sequences, which are essential for the ubiquitin-proteasome system’s function in protein degradation.* -
- Researchers compared ubiquitylation activities of various substrates and used techniques like biochemistry and crystallography to uncover how different E3 ligases from the KLHDCX family recognize C-degrons.* -
- Findings indicate that while a common anchoring motif aids in binding, variations in structure and additional interactions influence which substrates can be recognized and degraded, highlighting the complexity of substrate specificity.*
PROTAC® (proteolysis-targeting chimera) molecules induce proximity between an E3 ligase and protein-of-interest (POI) to target the POI for ubiquitin-mediated degradation. Cooperative E3-PROTAC-POI complexes have potential to achieve neo-substrate selectivity beyond that established by POI binding to the ligand alone. Here, we extend the collection of ubiquitin ligases employable for cooperative ternary complex formation to include the C-degron E3 KLHDC2.
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