ArticleMolecular cell2017
A General Strategy for Discovery of Inhibitors and Activators of RING and U-box E3 Ligases with Ubiquitin Variants.
Article in Molecular cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 77 citations in OpenAlex.
- Photocross-linking activity-based probes to capture the dynamics of ubiquitin RING E3 ligase interactions.The Biochemical journal · 2026Article
- E2 variants for probing E3 ubiquitin ligase activities.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Rice RING E3 Ligase OsRMT1 Negatively Regulates Salt Tolerance by Degrading the Canonical Salt-Responsive Protein OsMBL1.Plant biotechnology journal · 2025Article
- Tuning ubiquitin transfer by RING E3 ubiquitin ligases through the linchpin residue.Life science alliance · 2025Article
- Locking CBL TKBD in its native conformation presents a novel therapeutic opportunity in mutant CBL-dependent leukemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Chemical Tools for Probing the Ub/Ubl Conjugation Cascades.Chembiochem : a European journal of chemical biology · 2025Review
- Suppressing Tymovirus replication in plants using a variant of ubiquitin.PLoS pathogens · 2025Article
- Article
- UBE4B interacts with the ITCH E3 ubiquitin ligase to induce Ku70 and c-FLIPL polyubiquitination and enhanced neuroblastoma apoptosis.Cell death & disease · 2023Article
- Ubiquitin Engineering for Interrogating the Ubiquitin-Proteasome System and Novel Therapeutic Strategies.Cells · 2023Review
- Downregulation of UBE4B promotes CNS axon regrowth and functional recovery after stroke.iScience · 2023Article
- Fine-tuning of mTOR signaling by the UBE4B-KLHL22 E3 ubiquitin ligase cascade in brain development.Development (Cambridge, England) · 2022Article
- Praja1 RING-finger E3 ubiquitin ligase is a common suppressor of neurodegenerative disease-associated protein aggregation.Neuropathology : official journal of the Japanese Society of Neuropathology · 2022Article
- The DUB Club: Deubiquitinating Enzymes and Neurodevelopmental Disorders.Biological psychiatry · 2022Review
- On the Study of Deubiquitinases: Using the Right Tools for the Job.Biomolecules · 2022Review
- Panel of Engineered Ubiquitin Variants Targeting the Family of Human Ubiquitin Interacting Motifs.ACS chemical biology · 2022Article
- Structure of UBE2K-Ub/E3/polyUb reveals mechanisms of K48-linked Ub chain extension.Nature chemical biology · 2022Article
- Targeted Degradation of 53BP1 Using Ubiquitin Variant Induced Proximity.Biomolecules · 2022Article
- Article
- Ubiquitination in T-Cell Activation and Checkpoint Inhibition: New Avenues for Targeted Cancer Immunotherapy.International journal of molecular sciences · 2021Review
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
RING and U-box E3 ubiquitin ligases regulate diverse eukaryotic processes and have been implicated in numerous diseases, but targeting these enzymes remains a major challenge. We report the development of three ubiquitin variants (UbVs), each binding selectively to the RING or U-box domain of a distinct E3 ligase: monomeric UBE4B, phosphorylated active CBL, or dimeric XIAP. Structural and biochemical analyses revealed that UbVs specifically inhibited the activity of UBE4B or phosphorylated CBL by blocking the E2∼Ub binding site. Surprisingly, the UbV selective for dimeric XIAP formed a dimer to stimulate E3 activity by stabilizing the closed E2∼Ub conformation. We further verified the inhibitory and stimulatory functions of UbVs in cells. Our work provides a general strategy to inhibit or activate RING/U-box E3 ligases and provides a resource for the research community to modulate these enzymes.
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Registered trials
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.