ArticleThe EMBO journal2014
Autoubiquitination of the 26S proteasome on Rpn13 regulates breakdown of ubiquitin conjugates.
Article in The EMBO journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 175 citations in OpenAlex.
- Mapping the proteome landscape inPlant signaling & behavior · 2026Article
- Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.PLoS genetics · 2026Article
- Review
- Oxidative stress causes a reversible decrease of deubiquitylases activity in old vertebrate brains.Nature communications · 2026Article
- Mechanisms and Design Principles of Proteolysis-Targeting Chimeras and Their Emerging Applications.ACS pharmacology & translational science · 2026Review
- Acetic acid induces proteasome storage granule formation and inhibits proteasomal proteolysis: Comparison with other induction conditions.The Journal of biological chemistry · 2026Article
- In-situ cross-linking mass spectrometry reveals compartment-specific proteasomal interactions and structural heterogeneity.Nature communications · 2025Article
- The Radiation Sensitive 23B protein regulates root development partly through the E3 ubiquitin ligase EDA40.Plant cell reports · 2025Article
- Covalent inhibition ofiScience · 2025Article
- The ubiquitin-conjugating enzyme UBE2D maintains a youthful proteome and ensures protein quality control during aging by sustaining proteasome activity.PLoS biology · 2025Article
- Ubiquitin E3 ligases in the plant Arg/N-degron pathway.The Biochemical journal · 2024Review
- Temporal control of acute protein aggregate turnover by UBE3C and NRF1-dependent proteasomal pathways.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Pharmacologically increasing cGMP improves proteostasis and reduces neuropathy in mouse models of CMT1.Cellular and molecular life sciences : CMLS · 2024Article
- BIG enhances Arg/N-degron pathway-mediated protein degradation to regulate Arabidopsis hypoxia responses and suberin deposition.The Plant cell · 2024Article
- DNA damage-induced proteasome phosphorylation controls substrate recognition and facilitates DNA repair.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Specificity profiling of deubiquitylases against endogenously generated ubiquitin-protein conjugates.Cell chemical biology · 2024Article
- Dynamic molecular network analysis of iPSC-Purkinje cells differentiation delineates roles of ISG15 in SCA1 at the earliest stage.Communications biology · 2024Article
- Normal Proteasome Function Is Needed to Prevent Kidney Graft Injury during Cold Storage Followed by Transplantation.International journal of molecular sciences · 2024Article
- Adhesion-regulating molecule 1 (ADRM1) can be a potential biomarker and target for bladder cancer.Scientific reports · 2023Article
- Silencing of the 20S proteasomal subunit-α6 triggers full oogenesis arrest and increased mRNA levels of the selective autophagy adaptor protein p62/SQSTM1 in the ovary of the vector Rhodnius prolixus.PLoS neglected tropical diseases · 2023Article
49 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Degradation rates of most proteins in eukaryotic cells are determined by their rates of ubiquitination. However, possible regulation of the proteasome's capacity to degrade ubiquitinated proteins has received little attention, although proteasome inhibitors are widely used in research and cancer treatment. We show here that mammalian 26S proteasomes have five associated ubiquitin ligases and that multiple proteasome subunits are ubiquitinated in cells, especially the ubiquitin receptor subunit, Rpn13. When proteolysis is even partially inhibited in cells or purified 26S proteasomes with various inhibitors, Rpn13 becomes extensively and selectively poly-ubiquitinated by the proteasome-associated ubiquitin ligase, Ube3c/Hul5. This modification also occurs in cells during heat-shock or arsenite treatment, when poly-ubiquitinated proteins accumulate. Rpn13 ubiquitination strongly decreases the proteasome's ability to bind and degrade ubiquitin-conjugated proteins, but not its activity against peptide substrates. This autoinhibitory mechanism presumably evolved to prevent binding of ubiquitin conjugates to defective or stalled proteasomes, but this modification may also be useful as a biomarker indicating the presence of proteotoxic stress and reduced proteasomal capacity in cells or patients.
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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.