ArticleRSC chemical biology2021
Protein degradation profile reveals dynamic nature of 20S proteasome small molecule stimulation.
Article in RSC chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Synthetic-bioinformatic natural product-inspired peptides.Natural product reports · 2025Review
- Rpt5-Derived Analogs Stimulate Human Proteasome Activity in Cells and Degrade Proteins Forming Toxic Aggregates in Age-Related Diseases.International journal of molecular sciences · 2024Article
- Discovery and Development of Cyclic Peptide Proteasome Stimulators.Chembiochem : a European journal of chemical biology · 2024Article
- Proteasomal Stimulation by MK886 and Its Derivatives Can Rescue Tau-Induced Neurite Pathology.Molecular neurobiology · 2023Article
- High resolution structures define divergent and convergent mechanisms of archaeal proteasome activation.Communications biology · 2023Article
- Minimal mechanistic component of HbYX-dependent proteasome activation that reverses impairment by neurodegenerative-associated oligomers.Communications biology · 2023Article
- Depleting the 19S proteasome regulatory PSMD1 subunit as a cancer therapy strategy.Cancer medicine · 2023Article
- Minimal mechanistic component of HbYX-dependent proteasome activation.Research square · 2023Article
- Reversible protein assemblies in the proteostasis network in health and disease.Frontiers in molecular biosciences · 2023Review
- Oleic amide derivatives as small molecule stimulators of the human proteasome's core particle.RSC medicinal chemistry · 2022Article
- Solid-Phase Synthesis and Application of a Clickable Version of Epoxomicin for Proteasome Activity Analysis.Chembiochem : a European journal of chemical biology · 2022Article
- A Potential Mechanism for Targeting Aggregates With Proteasomes and Disaggregases in Liquid Droplets.Frontiers in aging neuroscience · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small molecules have been discovered to stimulate the 20S core particle (CP) of the proteasome to degrade proteins. However, the impact a 20S CP stimulator can have on the regulation of protein levels has not been fully characterized. Previous studies have focused on using one kind of stimulator to enhance the degradation of specific 20S CP substrates. We present here a study that utilizes several 20S CP stimulators to determine how each can affect the degradation of proteins in a biochemical assay with purified proteins and of an overexpressed GFP-fusion protein in cells. We also evaluate the effects of two stimulators on the whole cellular proteome in HEK-293T cells using label-free quantitative proteomic analysis for a broader understanding on their impact. Our studies demonstrate that 20S CP stimulation is likely to promote the degradation of significantly disordered proteins; however, the specific effect on the regulation of protein levels appears to be dependent on the mechanism of action of each stimulator due to the dynamic nature of the 20S CP. Our results reveal the potential of tailoring small molecule stimulators to influence the degradation of certain protein types and 20S CP substrates.
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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.