ArticleThe Journal of biological chemistry2012
Deconjugation of Nedd8 from Cul1 is directly regulated by Skp1-F-box and substrate, and the COP9 signalosome inhibits deneddylated SCF by a noncatalytic mechanism.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 120 citations in OpenAlex.
- Phosphorylation-dependent binding of the Adenomatous Polyposis Coli protein to β-TrCP1 regulates β-catenin destruction.bioRxiv : the preprint server for biology · 2026Article
- Protein neddylation as a therapeutic target: challenges and opportunities.The Journal of clinical investigation · 2026Review
- Cysteine availability tunes ubiquitin signaling via inverse stability of LRRC58 E3 ligase and its substrate CDO1.Nature communications · 2026Article
- Structural basis of CSN-mediated SCF deneddylation.Nature communications · 2026Article
- 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
- Mechanism of millisecond Lys48-linked poly-ubiquitin chain formation by cullin-RING ligases.Nature structural & molecular biology · 2024Article
- Dynamic molecular architecture and substrate recruitment of cullin3-RING E3 ligase CRL3Nature structural & molecular biology · 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
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- E3 ligase autoinhibition by C-degron mimicry maintains C-degron substrate fidelity.Molecular cell · 2023Article
- Plant deubiquitinases: from structure and activity to biological functions.Plant cell reports · 2023Review
- Activity-based profiling of cullin-RING ligase networks by conformation-specific probes.bioRxiv : the preprint server for biology · 2023Article
- Adaptive exchange sustains cullin-RING ubiquitin ligase networks and proper licensing of DNA replication.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Roles of Cullin-RING Ubiquitin Ligases in Cardiovascular Diseases.Biomolecules · 2022Review
- Co-adaptor driven assembly of a CUL3 E3 ligase complex.Molecular cell · 2022Article
- The CRL4The EMBO journal · 2021Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
COP9 signalosome (CSN) mediates deconjugation of the ubiquitin-like protein Nedd8 from the cullin subunits of SCF and other cullin-RING ubiquitin ligases (CRLs). This process is essential to maintain the proper activity of CRLs in cells. Here, we report a detailed kinetic characterization of CSN-mediated deconjugation of Nedd8 from SCF. CSN is an efficient enzyme, with a k(cat) of ~1 s(-1) and K(m) for neddylated Cul1-Rbx1 of ~200 nm, yielding a k(cat)/K(m) near the anticipated diffusion-controlled limit. Assembly with an F-box-Skp1 complex markedly inhibited deneddylation, although the magnitude varied considerably, with Fbw7-Skp1 inhibiting by ~5-fold but Skp2-Cks1-Skp1 by only ~15%. Deneddylation of both SCF(Fbw7) and SCF(Skp2-Cks1) was further inhibited ~2.5-fold by the addition of substrate. Combined, the inhibition by Fbw7-Skp1 plus its substrate cyclin E was greater than 10-fold. Unexpectedly, our results also uncover significant product inhibition by deconjugated Cul1, which results from the ability of Cul1 to bind tightly to CSN. Reciprocally, CSN inhibits the ubiquitin ligase activity of deneddylated Cul1. We propose a model in which assembled CRL complexes engaged with substrate are normally refractory to deneddylation. Upon consumption of substrate and subsequent deneddylation, CSN can remain stably bound to the CRL and hold it in low state of reduced activity.
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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.