ArticleNature2010
Enhancement of proteasome activity by a small-molecule inhibitor of USP14.
Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 578 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
578 citing papers in PubMed, 2 syntheses or guidelines pooled it, 921 citations in OpenAlex.
- The Emerging Roles of E3 Ligases and DUBs in Neurodegenerative Diseases.Molecular neurobiology · 2023Pooled it
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- DYT8 drives lung adenocarcinoma through EGFR-mediated PSMC6 recruitment and uncharacterized phosphorylation at Ser 306 and 525 of c-Src.Acta pharmacologica Sinica · 2026Article
- Substrate-Selective Inhibition of the SARS-CoV-2 Papain-Like Protease: Inhibition of Hydrolysis of Human Over Viral Substrates.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Therapeutics candidates and repurposing strategies to target parkinson's disease pathology: current evidence and future directions.Metabolic brain disease · 2026Review
- Decode the Ubiquitinome in Parkinson's Disease: From Pathological Aggregates to Targeted DUB Therapeutics.Neuroscience bulletin · 2026Review
- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- Kinetic control of macrophage death by PTM-turnover crosstalk in infection and inflammation.Cell chemical biology · 2026Review
- Emerging regulatory model of Ubiquitin-Specific Proteases 14 in cancer: from canonical oncogenesis to TME modulation, therapeutic resistance, and non-canonical activities.Journal of translational medicine · 2026Review
- Proteasome Dysfunction and Aggregation-Prone Proteins in Neurodegenerative Diseases: From Mechanisms to Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Targeting USP14 enhances immunotherapy response by reprogramming tumor-associated macrophages in colon cancer.iScience · 2026Article
- Mitochondria serve as a holdout compartment for aggregation-prone proteins hindering efficient degradation.Nature communications · 2026Article
- A High-Throughput Assay for Monitoring and Quantifying Amyloid-β Accumulation and Clearance in Alzheimer's Disease Cell Models.Journal of neurochemistry · 2026Article
- Oxidative stress causes a reversible decrease of deubiquitylases activity in old vertebrate brains.Nature communications · 2026Article
- Assessing the suitability of deubiquitylases as substrates for targeted protein degradation.Cell chemical biology · 2026Article
- Expanding the targeted protein degradation approach with small molecule chimeras directed to the 26S proteasome.Nature communications · 2026Article
- USP35 Acts as a Deubiquitinating Enzyme for ID3 to Promote Immune Escape in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Structural variations in evolutionary novel genomic regions: new insights into neurodevelopmental disorders by long-read DNA Sequencing.Molecular medicine (Cambridge, Mass.) · 2026Article
- Multidimensional analysis of deubiquitinating enzymes in colorectal cancer: biological mechanisms and targeted therapeutic strategies.Frontiers in oncology · 2026Review
- Dual targeting of the UPS and autophagy as a novel therapy for neurodegenerative proteinopathies.Frontiers in cellular neuroscience · 2026Review
518 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Proteasomes, the primary mediators of ubiquitin-protein conjugate degradation, are regulated through complex and poorly understood mechanisms. Here we show that USP14, a proteasome-associated deubiquitinating enzyme, can inhibit the degradation of ubiquitin-protein conjugates both in vitro and in cells. A catalytically inactive variant of USP14 has reduced inhibitory activity, indicating that inhibition is mediated by trimming of the ubiquitin chain on the substrate. A high-throughput screen identified a selective small-molecule inhibitor of the deubiquitinating activity of human USP14. Treatment of cultured cells with this compound enhanced degradation of several proteasome substrates that have been implicated in neurodegenerative disease. USP14 inhibition accelerated the degradation of oxidized proteins and enhanced resistance to oxidative stress. Enhancement of proteasome activity through inhibition of USP14 may offer a strategy to reduce the levels of aberrant proteins in cells under proteotoxic stress.
Indexed as
Identifiers
What OpenQuestion holds
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.