ArticleNature communications2019
Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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Who cites it
47 citing papers in PubMed, 64 citations in OpenAlex.
- Native Mass Spectrometry Analysis of Cullin-RING Ubiquitin E3 Ligase Complexes in the Context of Targeted Protein Degradation.Analytical chemistry · 2026Article
- A microprotein encoded by FERMT3 modulates endothelial cell protein catabolism and induces cell cycle arrest and senescence.Cell communication and signaling : CCS · 2026Article
- Upregulation of CSN8 induces a unique senescence-like state with robust tumor-promoting properties in epithelial ovarian cancer cells under hypoxia.Journal of translational medicine · 2026Article
- Article
- Interaction of CSN4 to DDB1 regulates its stability and function in DNA damage signaling.Cellular and molecular life sciences : CMLS · 2026Article
- The Degradation Pathway of COP9 Signalosome-Cullin-RING Ubiquitin Ligase Complexes via Autophagy.Biomolecules · 2026Article
- Structural basis of CSN-mediated SCF deneddylation.Nature communications · 2026Article
- Native Mass Spectrometry Analysis of Cullin RING Ubiquitin E3 Ligase Complexes in the Context of Targeted Protein Degradation.bioRxiv : the preprint server for biology · 2026Article
- Integrative Transcriptomics Identifies Ubiquitination-Related GenesJournal of inflammation research · 2026Article
- Orthosteric Molecular Glue Inhibits COP9 Signalosome with Substrate-Dependent Potency.bioRxiv : the preprint server for biology · 2025Article
- Global profiling of protein complex dynamics with an experimental library of protein interaction markers.Nature biotechnology · 2025Article
- Functional Characterization of Pathway Inhibitors for the Ubiquitin-Proteasome System (UPS) as Tool Compounds for CRBN and VHL-Mediated Targeted Protein Degradation.ACS chemical biology · 2025Article
- Advancing Cancer Immunotherapy through Engineering New PD-L1 Degraders: A Comprehensive Study from Small Molecules to PD-L1-Specific Peptide-Drug Conjugates.Journal of medicinal chemistry · 2024Article
- Noncanonical assembly, neddylation and chimeric cullin-RING/RBR ubiquitylation by the 1.8 MDa CUL9 E3 ligase complex.Nature structural & molecular biology · 2024Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- Dynamic molecular architecture and substrate recruitment of cullin3-RING E3 ligase CRL3Nature structural & molecular biology · 2024Article
- CAND1 inhibits Cullin-2-RING ubiquitin ligases for enhanced substrate specificity.Nature structural & molecular biology · 2024Article
- Computational exploration of the significance ofWorld journal of clinical oncology · 2023Article
- COPS6 promotes tumor progression and reduces CD8Acta pharmacologica Sinica · 2023Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Cullin-Ring E3 Ligases (CRLs) regulate a multitude of cellular pathways through specific substrate receptors. The COP9 signalosome (CSN) deactivates CRLs by removing NEDD8 from activated Cullins. Here we present structures of the neddylated and deneddylated CSN-CRL2 complexes by combining single-particle cryo-electron microscopy (cryo-EM) with chemical cross-linking mass spectrometry (XL-MS). These structures suggest a conserved mechanism of CSN activation, consisting of conformational clamping of the CRL2 substrate by CSN2/CSN4, release of the catalytic CSN5/CSN6 heterodimer and finally activation of the CSN5 deneddylation machinery. Using hydrogen-deuterium exchange (HDX)-MS we show that CRL2 activates CSN5/CSN6 in a neddylation-independent manner. The presence of NEDD8 is required to activate the CSN5 active site. Overall, by synergising cryo-EM with MS, we identify sensory regions of the CSN that mediate its stepwise activation and provide a framework for understanding the regulatory mechanism of other Cullin family members.
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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.