ArticleBiochemistry2018
Small Molecule Modulation of Proteasome Assembly.
Article in Biochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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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
40 citing papers in PubMed, 68 citations in OpenAlex.
- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- Beyond the structure-function paradigm: A comprehensive review of intrinsically disordered proteins.Biochemistry and biophysics reports · 2026Review
- Chemical Induction of MYC Protein Degradation via MYC-MAX Disruption and 20S Proteasome Activation.ACS chemical biology · 2026Article
- Proteasome Dysfunction and Aggregation-Prone Proteins in Neurodegenerative Diseases: From Mechanisms to Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- The causal relationship between multiple cardiovascular diseases and glioblastoma: A Mendelian randomization study.Medicine · 2026Article
- Tetra-anionic porphyrin mimics protein-protein interactions between regulatory particles and the catalytic core, allosterically activating human 20S proteasome.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Unveiling the Potential of a New β-Cyclodextrin-Suxibuzone Conjugate in Proteasome Regulation.ChemMedChem · 2025Article
- Recent Advancements in 20S Proteasome Enhancement: Degradation of Undruggable Targets.ACS medicinal chemistry letters · 2025Review
- Adaptive Suppression of MAPT Transcription Maintains Tau Proteostasis in Developing Human Neurons.Research square · 2025Article
- Targeted Degradation of Histone Deacetylases via Bypassing E3 Ligase Targeting Chimeras (BYETACs).ACS medicinal chemistry letters · 2025Article
- Blm10-Based Compounds Add to the Knowledge of How Allosteric Modulators Influence Human 20S Proteasome.ACS chemical biology · 2025Article
- Understanding neurodevelopmental proteasomopathies as new rare disease entities: A review of current concepts, molecular biomarkers, and perspectives.Genes & diseases · 2024Review
- 20S proteasome enhancers prevent cytotoxic tubulin polymerization-promoting protein induced α-synuclein aggregation.iScience · 2024Article
- Trehalose Promotes Clearance of Proteotoxic Aggregation of Neurodegenerative Disease-Associated Aberrant Proteins.Molecular neurobiology · 2024Article
- Proteasome Activators and Ageing: Restoring Proteostasis Using Small Molecules.Sub-cellular biochemistry · 2024Review
- Method of Monitoring 26S Proteasome in Cells Revealed the Crucial Role of PSMA3 C-Terminus in 26S Integrity.Biomolecules · 2023Article
- The ubiquitin-like modifier FAT10 is degraded by the 20S proteasome in vitro but not in cellulo.Life science alliance · 2023Article
- Development of a Cell-Based AlphaLISA Assay for High-Throughput Screening for Small Molecule Proteasome Modulators.ACS omega · 2023Article
- Depleting the 19S proteasome regulatory PSMD1 subunit as a cancer therapy strategy.Cancer medicine · 2023Article
- The Role of Intravesicular Proteins and the Protein Corona of Extracellular Vesicles in the Development of Drug-Induced Polyneuropathy.Current issues in molecular biology · 2023Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The 20S proteasome is the main protease that directly targets intrinsically disordered proteins (IDPs) for proteolytic degradation. Mutations, oxidative stress, or aging can induce the buildup of IDPs resulting in incorrect signaling or aggregation, associated with the pathogenesis of many cancers and neurodegenerative diseases. Drugs that facilitate 20S-mediated proteolysis therefore have many potential therapeutic applications. We report herein the modulation of proteasome assembly by the small molecule TCH-165, resulting in an increase in 20S levels. The increase in the level of free 20S corresponds to enhanced proteolysis of IDPs, including α-synuclein, tau, ornithine decarboxylase, and c-Fos, but not structured proteins. Clearance of ubiquitinated protein was largely maintained by single capped proteasome complexes (19S-20S), but accumulation occurs when all 19S capped proteasome complexes are depleted. This study illustrates the first example of a small molecule capable of targeting disordered proteins for degradation by regulating the dynamic equilibrium between different proteasome complexes.
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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.