ArticleMolecular systems biology2024
Systematic identification of 20S proteasome substrates.
Article in Molecular systems biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- The ubiquitin-proteasome system and autophagy as guardians of the cellular proteome.FEBS letters · 2026Review
- BAG2 Condensates Couple Proteostasis to CD8bioRxiv : the preprint server for biology · 2026Article
- Acetic acid induces proteasome storage granule formation and inhibits proteasomal proteolysis: Comparison with other induction conditions.The Journal of biological chemistry · 2026Article
- 3D Proteomics: Structural, Functional, Chemical and Biomarker Discovery Proteomics With LiP-MS.Molecular & cellular proteomics : MCP · 2026Review
- APOL1 plasma membrane pools resist rapid protein degradation.Scientific reports · 2026Article
- Sorbic acid triggers rapid formation of proteasome storage granules inMicrobial cell (Graz, Austria) · 2026Article
- Mild traumatic brain injury promotes chronic cerebrovascular inflammation and glymphatic suppression.Molecular neurodegeneration advances · 2026Article
- Hyperactive 20Science advances · 2025Article
- Proteasome-derived peptides: separating the trash from the recycling.Trends in biochemical sciences · 2025Review
- 19S proteasome loss regulates mitotic spindle assembly through a ubiquitin-independent degradation mechanism.Cell reports · 2025Article
- Ubiquitin-Proteasome System Dysregulation in Alzheimer's Disease Impacts Protein Abundance.bioRxiv : the preprint server for biology · 2025Article
- Tracking proteasome degradation: A cross-organ analysis via intact degradomics mass spectrometry.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Ubiquitin-Independent Degradation: An Emerging PROTAC Approach?BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Activation of the 26S Proteasome to Reduce Proteotoxic Stress and Improve the Efficacy of PROTACs.ACS pharmacology & translational science · 2025Review
- 19S proteasome loss causes monopolar spindles through ubiquitin-independent KIF11 degradation.bioRxiv : the preprint server for biology · 2025Article
- Emerging concepts and treatments in autoinflammatory interferonopathies and monogenic systemic lupus erythematosus.Nature reviews. Rheumatology · 2025Review
- Parthanatos drives cognitive decline in repeated brain trauma: MSC-derived exosomes as a novel therapeutic strategy.Frontiers in pharmacology · 2025Article
- Functional 20S Proteasomes in Retroviruses: Evidence in Favor.International journal of molecular sciences · 2024Article
- ProEnd: a comprehensive database for identifying HbYX motif-containing proteins across the tree of life.BMC genomics · 2024Article
- ProEnd: A Comprehensive Database for Identifying HbYX Motif-Containing Proteins Across the Tree of Life.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
For years, proteasomal degradation was predominantly attributed to the ubiquitin-26S proteasome pathway. However, it is now evident that the core 20S proteasome can independently target proteins for degradation. With approximately half of the cellular proteasomes comprising free 20S complexes, this degradation mechanism is not rare. Identifying 20S-specific substrates is challenging due to the dual-targeting of some proteins to either 20S or 26S proteasomes and the non-specificity of proteasome inhibitors. Consequently, knowledge of 20S proteasome substrates relies on limited hypothesis-driven studies. To comprehensively explore 20S proteasome substrates, we employed advanced mass spectrometry, along with biochemical and cellular analyses. This systematic approach revealed hundreds of 20S proteasome substrates, including proteins undergoing specific N- or C-terminal cleavage, possibly for regulation. Notably, these substrates were enriched in RNA- and DNA-binding proteins with intrinsically disordered regions, often found in the nucleus and stress granules. Under cellular stress, we observed reduced proteolytic activity in oxidized proteasomes, with oxidized protein substrates exhibiting higher structural disorder compared to unmodified proteins. Overall, our study illuminates the nature of 20S substrates, offering crucial insights into 20S proteasome biology.
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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.