ArticleStructure (London, England : 1993)2018
A Structure-Based Strategy for Engineering Selective Ubiquitin Variant Inhibitors of Skp1-Cul1-F-Box Ubiquitin Ligases.
Article in Structure (London, England : 1993), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 34 citations in OpenAlex.
- Protist oxygen-sensing and the role of prolyl hydroxylase-regulation of E3(SCF) ubiquitin ligases.Biochimica et biophysica acta. General subjects · 2026Review
- Proteasome activity maintains cell-type-specific gene expression.Cell reports · 2026Article
- Glycoregulation of E3(SCF) ubiquitin ligases in unicellular eukaryotes.Glycobiology · 2025Review
- Inhibition of SCFCommunications biology · 2025Article
- Article
- Ubiquitin Engineering for Interrogating the Ubiquitin-Proteasome System and Novel Therapeutic Strategies.Cells · 2023Review
- Targeted Degradation of 53BP1 Using Ubiquitin Variant Induced Proximity.Biomolecules · 2022Article
- Structural and functional characterization of ubiquitin variant inhibitors for the JAMM-family deubiquitinases STAMBP and STAMBPL1.The Journal of biological chemistry · 2021Article
- KDM2B Overexpression Facilitates LyticJournal of virology · 2021Article
- Molecular Characterization, Gene Evolution and Expression Analysis of the F-Box Gene Family in Tomato (Genes · 2021Article
- [Effects of Cullin1 on the Biological Characteristics of Lung Adenocarcinoma A549 and H1395 Cells].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Article
- Protein Engineering in the Ubiquitin System: Tools for Discovery and Beyond.Pharmacological reviews · 2020Review
- Genome-wide analysis and characterization of F-box gene family in Gossypium hirsutum L.BMC genomics · 2019Article
- Protein engineering of a ubiquitin-variant inhibitor of APC/C identifies a cryptic K48 ubiquitin chain binding site.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Emerging drug development technologies targeting ubiquitination for cancer therapeutics.Pharmacology & therapeutics · 2019Review
- The ubiquitin interacting motifs of USP37 act on the proximal Ub of a di-Ub chain to enhance catalytic efficiency.Scientific reports · 2019Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
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Abstract
Skp1-Cul1-F-box (SCF) E3 ligases constitute the largest and best-characterized family of the multisubunit E3 ligases with important cellular functions and numerous disease links. The specificity of an SCF E3 ligase is established by one of the 69 human F-box proteins that are recruited to Cul1 through the Skp1 adaptor. We previously reported generation of ubiquitin variants (UbVs) targeting Fbw7 and Fbw11, which inhibit ligase activity by binding at the F-box-Skp1 interface to competitively displace Cul1. In the present study, we employed an optimized engineering strategy to generate specific binding UbVs against 17 additional Skp1-F-box complexes. We validated our design strategy and uncovered the structural basis of binding specificity by crystallographic analyses of representative UbVs bound to Skp1-Fbl10 and Skp1-Fbl11. Our study highlights the power of combining phage display with structure-based design to develop UbVs targeting specific protein surfaces.
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