ArticleeLife2016
Structural and kinetic analysis of the COP9-Signalosome activation and the cullin-RING ubiquitin ligase deneddylation cycle.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
63 citing papers in PubMed.
- Arabidopsis inositol polyphosphate kinase activities regulate COP9 deneddylation functions in phosphate homeostasis.Journal of integrative plant biology · 2026Article
- Protist oxygen-sensing and the role of prolyl hydroxylase-regulation of E3(SCF) ubiquitin ligases.Biochimica et biophysica acta. General subjects · 2026Review
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- Article
- 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
- Cul5: immune cell function and therapeutic potential.Frontiers in immunology · 2026Review
- Orthosteric Molecular Glue Inhibits COP9 Signalosome with Substrate-Dependent Potency.bioRxiv : the preprint server for biology · 2025Article
- A diverse family of bacterial deubiquitinases is defined by theProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular mechanisms of CAND2 in regulating SCF ubiquitin ligases.Nature communications · 2025Article
- 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
- Cullin-RING ligases employ geometrically optimized catalytic partners for substrate targeting.Molecular cell · 2024Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- CAND1 inhibits Cullin-2-RING ubiquitin ligases for enhanced substrate specificity.Nature structural & molecular biology · 2024Article
- Dynamic molecular architecture and substrate recruitment of cullin3-RING E3 ligase CRL3Nature structural & molecular biology · 2024Article
- Mechanism of millisecond Lys48-linked poly-ubiquitin chain formation by cullin-RING ligases.Nature structural & molecular biology · 2024Article
- SMC5/6 Promotes Replication Fork Stability via Negative Regulation of the COP9 Signalosome.International journal of molecular sciences · 2024Article
- Activity-based profiling of cullin-RING E3 networks by conformation-specific probes.Nature chemical biology · 2023Article
- The C-terminal tail of CSNAP attenuates the CSN complex.Life science alliance · 2023Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
The COP9-Signalosome (CSN) regulates cullin-RING ubiquitin ligase (CRL) activity and assembly by cleaving Nedd8 from cullins. Free CSN is autoinhibited, and it remains unclear how it becomes activated. We combine structural and kinetic analyses to identify mechanisms that contribute to CSN activation and Nedd8 deconjugation. Both CSN and neddylated substrate undergo large conformational changes upon binding, with important roles played by the N-terminal domains of Csn2 and Csn4 and the RING domain of Rbx1 in enabling formation of a high affinity, fully active complex. The RING domain is crucial for deneddylation, and works in part through conformational changes involving insert-2 of Csn6. Nedd8 deconjugation and re-engagement of the active site zinc by the autoinhibitory Csn5 glutamate-104 diminish affinity for Cul1/Rbx1 by ~100-fold, resulting in its rapid ejection from the active site. Together, these mechanisms enable a dynamic deneddylation-disassembly cycle that promotes rapid remodeling of the cellular CRL network.
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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.