ArticleGenes & development2004
VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases.
Article in Genes & development, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 285 papers.
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Who cites it
285 citing papers in PubMed, 480 citations in OpenAlex.
- Structure of the E3 ligase CRL2Cell reports · 2026Article
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- A testis-specific E3 ubiquitin ligase complex governs spermiogenesis and male fertility.Nature communications · 2026Article
- The E3 ubiquitin ligase mechanism specifying target-directed microRNA degradation.bioRxiv : the preprint server for biology · 2026Article
- CUL5-mediated ubiquitination in cancer cell therapy: context-dependent roles, molecular networks, and emerging therapeutic avenues.Frontiers in medicine · 2026Review
- TOM20-driven E3 ligase recruitment regulates mitochondrial dynamics through PLD6.Nature chemical biology · 2026Article
- SOCS1 depletion drives osteosarcoma stemness and chemoresistance by suppressing ACTN4 degradation.Acta pharmacologica Sinica · 2026Article
- Regulatory Mechanisms of miRNA Turnover: Insights into ZSWIM8-Mediated Target-Directed MicroRNA Degradation.Biomedicines · 2025Review
- In-cell proximity target validation methods for heterobifunctional molecules with CRBN- or VHL-binder using AirID.Communications biology · 2025Article
- A novel oncogene, leucine-rich repeat protein 1, mediates hypoxia-induced hepatocellular carcinoma progression.Functional & integrative genomics · 2025Article
- Characteristics of the Kelch domain containing (KLHDC) subfamily and relationships with diseases.FEBS letters · 2025Review
- Cullin-RING Ubiquitin Ligases in Neurodevelopment and Neurodevelopmental Disorders.Biomedicines · 2025Review
- Nutrient restriction protects against valve interstitial cell calcification by upregulating ubiquitin mediated proteolysis.Frontiers in cardiovascular medicine · 2025Article
- Structural basis for C-degron selectivity across KLHDCX family E3 ubiquitin ligases.Nature communications · 2024Article
- Molecular insights into degron recognition by CRL5Nature communications · 2024Article
- A recurrent missense variant in the E3 ubiquitin ligase substrate recognition subunit FEM1B causes a rare syndromic neurodevelopmental disorder.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Cullin-RING ligases employ geometrically optimized catalytic partners for substrate targeting.Molecular cell · 2024Article
- PROTACs: Current and Future Potential as a Precision Medicine Strategy to Combat Cancer.Molecular cancer therapeutics · 2024Review
- Review
- CAND1 inhibits Cullin-2-RING ubiquitin ligases for enhanced substrate specificity.Nature structural & molecular biology · 2024Article
225 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ECS (Elongin B/C-Cul2/Cul5-SOCS-box protein) complex is a member of a family of ubiquitin ligases that share a Cullin-Rbx module. SOCS-box proteins recruit substrates to the ECS complex and are linked to Cullin-Rbx via Elongin B/C. VHL has been implicated as a SOCS-box protein, but lacks a C-terminal sequence (downstream of the BC box) of the SOCS box. We now show that VHL specifically interacts with endogenous Cul2-Rbx1 in mammalian cells, whereas SOCS-box proteins associate with Cul5-Rbx2. We also identify LRR-1 and FEM1B as proteins that share a region of homology with VHL (the VHL box, including the BC box and downstream residues) and associate with Cul2-Rbx1. ECS complexes can thus be classified into two distinct protein assemblies, that is, those that contain a subunit with a VHL box (composed of the BC box and a downstream Cul2 box) that interacts with Cul2-Rbx1, and those that contain a subunit with a SOCS box (BC box and downstream Cul5 box) that interacts with Cul5-Rbx2. Domain-swapping analyses showed that the specificity of interaction of VHL-box and SOCS-box proteins with Cullin-Rbx modules is determined by the Cul2 and Cul5 boxes, respectively. Finally, RNAi-mediated knockdown of the Cul2-Rbx1 inhibited the VHL-mediated degradation of HIF-2alpha, whereas knockdown of Cul5-Rbx2 did not affect it. These data suggest that the functions of the Cul2-Rbx1 and Cul5-Rbx2 modules are distinct.
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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.