ArticleMolecular cell2024
Cullin-RING ligases employ geometrically optimized catalytic partners for substrate targeting.
Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Induced ubiquitination of the partially disordered estrogen receptor alpha via a 14-3-3 directed molecular glue-PROTAC.Nature communications · 2026Article
- Native Mass Spectrometry Analysis of Cullin-RING Ubiquitin E3 Ligase Complexes in the Context of Targeted Protein Degradation.Analytical chemistry · 2026Article
- Structure of the E3 ligase CRL2Cell reports · 2026Article
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Cysteine availability tunes ubiquitin signaling via inverse stability of LRRC58 E3 ligase and its substrate CDO1.Nature communications · 2026Article
- FBXL6 promotes bladder cancer progression by stabilizing ENO1 through K63-linked ubiquitination.Cell death discovery · 2026Article
- Survey of the human proteostasis network: the ubiquitin-proteasome system.bioRxiv : the preprint server for biology · 2026Article
- Structural basis of NSD2 degradation via targeted recruitment of SCF-FBXO22.Nature communications · 2026Article
- Native Mass Spectrometry Analysis of Cullin RING Ubiquitin E3 Ligase Complexes in the Context of Targeted Protein Degradation.bioRxiv : the preprint server for biology · 2026Article
- E2 variants for probing E3 ubiquitin ligase activities.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Chemically-induced degradation of the endoplasmic-reticulum stress sensor IRE1 by a VHL-recruiting chimera.Nature communications · 2025Article
- E3 ubiquitin ligases in signaling, disease, and therapeutics.Trends in biochemical sciences · 2025Review
- Thioether-mediated protein ubiquitination in constructing affinity- and activity-based ubiquitinated protein probes.Nature protocols · 2025Review
- Structural insights into CRL2FEM1C ubiquitin ligase-mediated protein ubiquitination.Journal of molecular cell biology · 2025Article
- Targeted protein degradation for cancer therapy.Nature reviews. Cancer · 2025Review
- BiDAC-dependent degradation of plasma membrane proteins by the endolysosomal system.Nature communications · 2025Article
- DET1 dynamics underlie cooperative ubiquitination by CRL4Science advances · 2025Article
- Identification of novel 7-hydroxycoumarin derivatives as ELOC binders with potential to modulate CRL2 complex formation.Scientific reports · 2025Article
- A Kinetic Scout Approach Accelerates Targeted Protein Degrader Development.Angewandte Chemie (International ed. in English) · 2025Article
- Activation of the 26S Proteasome to Reduce Proteotoxic Stress and Improve the Efficacy of PROTACs.ACS pharmacology & translational science · 2025Review
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Cullin-RING ligases (CRLs) ubiquitylate specific substrates selected from other cellular proteins. Substrate discrimination and ubiquitin transferase activity were thought to be strictly separated. Substrates are recognized by substrate receptors, such as Fbox or BCbox proteins. Meanwhile, CRLs employ assorted ubiquitin-carrying enzymes (UCEs, which are a collection of E2 and ARIH-family E3s) specialized for either initial substrate ubiquitylation (priming) or forging poly-ubiquitin chains. We discovered specific human CRL-UCE pairings governing substrate priming. The results reveal pairing of CUL2-based CRLs and UBE2R-family UCEs in cells, essential for efficient PROTAC-induced neo-substrate degradation. Despite UBE2R2's intrinsic programming to catalyze poly-ubiquitylation, CUL2 employs this UCE for geometrically precise PROTAC-dependent ubiquitylation of a neo-substrate and for rapid priming of substrates recruited to diverse receptors. Cryo-EM structures illuminate how CUL2-based CRLs engage UBE2R2 to activate substrate ubiquitylation. Thus, pairing with a specific UCE overcomes E2 catalytic limitations to drive substrate ubiquitylation and targeted protein degradation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.