ArticleJournal of molecular biology2009
Proteasomes can degrade a significant proportion of cellular proteins independent of ubiquitination.
Article in Journal of molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers, 1 of them a synthesis that pooled it.
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Who cites it
129 citing papers in PubMed, 1 synthesis or guideline pooled it, 215 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Exploring the sex-dependent effects of midnolin loss on hepatic transcription and chromatin accessibility.Biochemistry and biophysics reports · 2026Article
- Salivary Proteins of Whitefly Bemisia tabaci Modulate Plant Defenses by Activating SA Signaling Pathway.Archives of insect biochemistry and physiology · 2026Article
- The ubiquitin-proteasome system and autophagy as guardians of the cellular proteome.FEBS letters · 2026Review
- Proteasomal control of transcription factors: mechanisms, regulation and dysregulation.Cellular and molecular life sciences : CMLS · 2026Review
- Oncogenic KRAS/ERK/JUNB signaling suppresses differentiation regulator GATA6 in pancreatic cancer.The Journal of clinical investigation · 2026Article
- Breaking the proteasome balance: α-synuclein and the ubiquitin-proteasome system.Frontiers in cell and developmental biology · 2026Review
- Dual targeting of the UPS and autophagy as a novel therapy for neurodegenerative proteinopathies.Frontiers in cellular neuroscience · 2026Review
- PPM1D is directly degraded by proteasomes in a ubiquitination-independent manner through its carboxyl-terminal region.Journal of biomedical science · 2025Article
- pVHL regulates protein stability of the TCF/LEF transcription factor family via ubiquitin-independent proteasomal degradation.Cellular and molecular life sciences : CMLS · 2025Article
- Not Just PA28γ: What We Know About the Role of PA28αβ in Carcinogenesis.Biomolecules · 2025Review
- Mutational pressure promotes release of public CD8iScience · 2025Article
- Mechanisms and regulation of substrate degradation by the 26S proteasome.Nature reviews. Molecular cell biology · 2025Review
- Ubiquitin-Independent Degradation: An Emerging PROTAC Approach?BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- NeoDesign: a computational tool for optimal selection of polyvalent neoantigen combinations.Bioinformatics (Oxford, England) · 2024Article
- The hydrophobicity of the CARD8 N-terminus tunes inflammasome activation.Cell chemical biology · 2024Article
- The interaction between NLRP1 and oxidized TRX1 involves a transient disulfide bond.Cell chemical biology · 2024Article
- Systematic identification of 20S proteasome substrates.Molecular systems biology · 2024Article
- Structure basis for recognition of plant Rpn10 by phytoplasma SAP05 in ubiquitin-independent protein degradation.iScience · 2024Article
- Proteasome Activators and Ageing: Restoring Proteostasis Using Small Molecules.Sub-cellular biochemistry · 2024Review
69 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The critical role of the ubiquitin-26S proteasome system in regulation of protein homeostasis in eukaryotes is well established. In contrast, the impact of the ubiquitin-independent proteolytic activity of proteasomes is poorly understood. Through biochemical analysis of mammalian lysates, we find that the 20S proteasome, latent in peptide hydrolysis, specifically cleaves more than 20% of all cellular proteins. Thirty intrinsic proteasome substrates (IPSs) were identified and in vitro studies of their processing revealed that cleavage occurs at disordered regions, generating stable products encompassing structured domains. The mechanism of IPS recognition is remarkably well conserved in the eukaryotic kingdom, as mammalian and yeast 20S proteasomes exhibit the same target specificity. Further, 26S proteasomes specifically recognize and cleave IPSs at similar sites, independent of ubiquitination, suggesting that disordered regions likely constitute the universal structural signal for IPS proteolysis by proteasomes. Finally, we show that proteasomes contribute to physiological regulation of IPS levels in living cells and the inactivation of ubiquitin-activating enzyme E1 does not prevent IPS degradation. Collectively, these findings suggest a significant contribution of the ubiquitin-independent proteasome degradation pathway to the regulation of protein homeostasis in eukaryotes.
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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.