ArticleeLife2019
Robust cullin-RING ligase function is established by a multiplicity of poly-ubiquitylation pathways.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 80 citations in OpenAlex.
- Induced ubiquitination of the partially disordered estrogen receptor alpha via a 14-3-3 directed molecular glue-PROTAC.Nature communications · 2026Article
- Cysteine availability tunes ubiquitin signaling via inverse stability of LRRC58 E3 ligase and its substrate CDO1.Nature communications · 2026Article
- Snord15b Maintains Stemness of Intestinal Stem Cells via Enhancement of Alternative Splicing of Btrc Short Isoform for Suppression of β-Catenin Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Piceatannol Attenuates Benzo[Journal of agricultural and food chemistry · 2025Article
- Structural basis for C-degron selectivity across KLHDCX family E3 ubiquitin ligases.Nature communications · 2024Article
- A Novel Confocal Scanning Protein-Protein Interaction Assay (PPI-CONA) Reveals Exceptional Selectivity and Specificity of CC0651, a Small Molecule Binding Enhancer of the Weak Interaction between the E2 Ubiquitin-Conjugating Enzyme CDC34A and Ubiquitin.Bioconjugate chemistry · 2024Article
- The emerging roles of non-canonical ubiquitination in proteostasis and beyond.The Journal of cell biology · 2024Review
- Structure and dynamics of a pentameric KCTD5/CUL3/Gβγ E3 ubiquitin ligase complex.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Cullin-RING ligases employ geometrically optimized catalytic partners for substrate targeting.Molecular cell · 2024Article
- Noncanonical and reversible cysteine ubiquitination prevents the overubiquitination of PEX5 at the peroxisomal membrane.PLoS biology · 2024Article
- Mechanism of millisecond Lys48-linked poly-ubiquitin chain formation by cullin-RING ligases.Nature structural & molecular biology · 2024Article
- Catalysis of non-canonical protein ubiquitylation by the ARIH1 ubiquitin ligase.The Biochemical journal · 2023Article
- Real-time bio-layer interferometry ubiquitination assays as alternatives to western blotting.Analytical biochemistry · 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
- Structure of CRL7Nature structural & molecular biology · 2022Article
- Article
- Clinical significance of FBXW7 loss of function in human cancers.Molecular cancer · 2022Review
- Identification and optimization of molecular glue compounds that inhibit a noncovalent E2 enzyme-ubiquitin complex.Science advances · 2021Article
- TIMELESS-TIPIN and UBXN-3 promote replisome disassembly during DNA replication termination in Caenorhabditis elegans.The EMBO journal · 2021Article
- Cullin-RING Ubiquitin Ligase Regulatory Circuits: A Quarter Century Beyond the F-Box Hypothesis.Annual review of biochemistry · 2021Review
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
The cullin-RING ligases (CRLs) form the major family of E3 ubiquitin ligases. The prototypic CRLs in yeast, called SCF enzymes, employ a single E2 enzyme, Cdc34, to build poly-ubiquitin chains required for degradation. In contrast, six different human E2 and E3 enzyme activities, including Cdc34 orthologs UBE2R1 and UBE2R2, appear to mediate SCF-catalyzed substrate polyubiquitylation in vitro. The combinatorial interplay of these enzymes raises questions about genetic buffering of SCFs in human cells and challenges the dogma that E3s alone determine substrate specificity. To enable the quantitative comparisons of SCF-dependent ubiquitylation reactions with physiological enzyme concentrations, mass spectrometry was employed to estimate E2 and E3 levels in cells. In combination with UBE2R1/2, the E2 UBE2D3 and the E3 ARIH1 both promoted SCF-mediated polyubiquitylation in a substrate-specific fashion. Unexpectedly, UBE2R2 alone had negligible ubiquitylation activity at physiological concentrations and the ablation of UBE2R1/2 had no effect on the stability of SCF substrates in cells. A genome-wide CRISPR screen revealed that an additional E2 enzyme, UBE2G1, buffers against the loss of UBE2R1/2. UBE2G1 had robust in vitro chain extension activity with SCF, and UBE2G1 knockdown in cells lacking UBE2R1/2 resulted in stabilization of the SCF substrates p27 and CYCLIN E as well as the CUL2-RING ligase substrate HIF1α. The results demonstrate the human SCF enzyme system is diversified by association with multiple catalytic enzyme partners.
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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.