ArticleNature communications2016
Targeted inhibition of the COP9 signalosome for treatment of cancer.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 3 of them syntheses that pooled it.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
109 citing papers in PubMed, 3 syntheses or guidelines pooled it, 197 citations in OpenAlex.
- Prognostic value of CSN5 in patients with digestive system cancers: a systematic review and meta-analysis.BMC cancer · 2022Pooled it
- Prognostic role of c-Jun activation domain-binding protein-1 in cancer: A systematic review and meta-analysis.Journal of cellular and molecular medicine · 2021Pooled it
- Cullin Deneddylation Suppresses the Necroptotic Pathway in Cardiomyocytes.Frontiers in physiology · 2021Pooled it
- Arabidopsis inositol polyphosphate kinase activities regulate COP9 deneddylation functions in phosphate homeostasis.Journal of integrative plant biology · 2026Article
- Ubiquitin family as novel protein partners for molecular glues.npj drug discovery · 2026Review
- Protein neddylation as a therapeutic target: challenges and opportunities.The Journal of clinical investigation · 2026Review
- COP9 signalosome regulates EGFR and Notch signaling during myeloid-type progenitor cell fate decision in Drosophila.EMBO reports · 2026Article
- COP9 signalosome deneddylation activity is required for proliferation but not dedifferentiation of vascular smooth muscle cells in neointimal hyperplasia.American journal of physiology. Heart and circulatory physiology · 2026Article
- The role of ubiquitin system in ageing-related diseases and potential therapeutic opportunities.Molecular biomedicine · 2026Review
- CAND1 and CAND2 drive CUL4 substrate receptor exchange with largely comparable biochemical efficiency, unlike their relative effects on CUL1.Structure (London, England : 1993) · 2026Article
- K63-linked ubiquitylation of S2P-RNAPII regulates transcription in a DNAPK inter-dependent manner in response to double-strand breaks.Nucleic acids research · 2026Article
- Article
- Interaction of CSN4 to DDB1 regulates its stability and function in DNA damage signaling.Cellular and molecular life sciences : CMLS · 2026Article
- Human DNA polymerase η is regulated by mutually exclusive mono-ubiquitination and mono-NEDDylation.Nucleic acids research · 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
- Utilization of Functional Degradation Pathways for the Characterization of Ubiquitin-Proteasome System Tool Compounds.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Versatile roles of inositol hexakisphosphate in the ubiquitin-proteasome system.Essays in biochemistry · 2025Review
- Orthosteric Molecular Glue Inhibits COP9 Signalosome with Substrate-Dependent Potency.bioRxiv : the preprint server for biology · 2025Article
- COPS5 inhibition synergizes with the antitumor effect of trastuzumab by PTEN upregulation in HER2-amplified gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The COP9 signalosome (CSN) is a central component of the activation and remodelling cycle of cullin-RING E3 ubiquitin ligases (CRLs), the largest enzyme family of the ubiquitin-proteasome system in humans. CRLs are implicated in the regulation of numerous cellular processes, including cell cycle progression and apoptosis, and aberrant CRL activity is frequently associated with cancer. Remodelling of CRLs is initiated by CSN-catalysed cleavage of the ubiquitin-like activator NEDD8 from CRLs. Here we describe CSN5i-3, a potent, selective and orally available inhibitor of CSN5, the proteolytic subunit of CSN. The compound traps CRLs in the neddylated state, which leads to inactivation of a subset of CRLs by inducing degradation of their substrate recognition module. CSN5i-3 differentially affects the viability of tumour cell lines and suppresses growth of a human xenograft in mice. Our results provide insights into how CSN regulates CRLs and suggest that CSN5 inhibition has potential for anti-tumour therapy.
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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.