ArticleNature communications2022
Structural basis for specific inhibition of the deubiquitinase UCHL1.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Balancing Ubiquitination and Deubiquitination in Apoptotic Protein Stability and Cancer Cell Survival.International journal of molecular sciences · 2026Review
- UCHL1-mediated deubiquitination of PARK7 suppresses ferroptosis and enhances tumor progression in triple-negative breast cancer.Molecular and cellular biochemistry · 2026Article
- Comprehensive Chemoproteomics Unveils Selective HMG-CoA Synthase 1 Inhibitors for Targeting Mevalonate Metabolism in Cancer.Journal of the American Chemical Society · 2026Article
- From Covalent Traps to Fluorescent Beacons: The Expanding Arsenal of Chemical Probes for Studying Ubiquitin and Ubiquitin-Like Proteins.Angewandte Chemie (International ed. in English) · 2026Review
- High-Throughput Synthesis and Screening of a Cyanimide Library Identifies Selective Inhibitors of ISG15-Specific Protease mUSP18.Angewandte Chemie (International ed. in English) · 2025Article
- Chimeric deubiquitinase engineering reveals structural basis for specific inhibition of the mitophagy regulator USP30.Nature structural & molecular biology · 2025Article
- The mitochondrial hub gene UCHL1 May serve as a potential biomarker for diagnosing diabetic cardiomyopathy: a comprehensive integration of biological pathways.BMC medical genomics · 2025Article
- Effect of deubiquitinases in head and neck squamous cell carcinoma (Review).Oncology letters · 2025Review
- Enantioselective OTUD7B fragment discovery through chemoproteomics screening and high-throughput optimisation.Communications chemistry · 2025Article
- Review
- Open-source electrophilic fragment screening platform to identify chemical starting points for UCHL1 covalent inhibitors.SLAS discovery : advancing life sciences R & D · 2024Article
- Scalable Thiol Reactivity Profiling Identifies Azetidinyl Oxadiazoles as Cysteine-Targeting Electrophiles.Journal of the American Chemical Society · 2024Article
- DUBs in Alzheimer's disease: mechanisms and therapeutic implications.Cell death discovery · 2024Review
- The role of ubiquitination in health and disease.MedComm · 2024Review
- Discovery of potent and selective activity-based probes (ABPs) for the deubiquitinating enzyme USP30.RSC chemical biology · 2024Article
- Altered Protein Dynamics and a More Reactive Catalytic Cysteine in a Neurodegeneration-associated UCHL1 Mutant.Journal of molecular biology · 2024Article
- Bactericidal bissulfone BScience China. Life sciences · 2024Article
- Ubiquitin Carboxyl-Terminal Hydrolase L1 and Its Role in Parkinson's Disease.International journal of molecular sciences · 2024Review
- Potential roles of UCH family deubiquitinases in tumorigenesis and chemical inhibitors developed against them.American journal of cancer research · 2024Review
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ubiquitination regulates protein homeostasis and is tightly controlled by deubiquitinases (DUBs). Loss of the DUB UCHL1 leads to neurodegeneration, and its dysregulation promotes cancer metastasis and invasiveness. Small molecule probes for UCHL1 and DUBs in general could help investigate their function, yet specific inhibitors and structural information are rare. Here we report the potent and non-toxic chemogenomic pair of activity-based probes GK13S and GK16S for UCHL1. Biochemical characterization of GK13S demonstrates its stereoselective inhibition of cellular UCHL1. The crystal structure of UCHL1 in complex with GK13S shows the enzyme locked in a hybrid conformation of apo and Ubiquitin-bound states, which underlies its UCHL1-specificity within the UCH DUB family. Phenocopying a reported inactivating mutation of UCHL1 in mice, GK13S, but not GK16S, leads to reduced levels of monoubiquitin in a human glioblastoma cell line. Collectively, we introduce a set of structurally characterized, chemogenomic probes suitable for the cellular investigation of UCHL1.
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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.