ArticleACS synthetic biology2023
Receptor Elimination by E3 Ubiquitin Ligase Recruitment (REULR): A Targeted Protein Degradation Toolbox.
Article in ACS synthetic biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 47 citations in OpenAlex.
- Engineering Antibodies into Targeted Chimeras: From Recognition Modules to Programmable Degraders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Nanotechnology-Enabled Targeted Protein Degradation: Strategies, Opportunities, and Challenges.Small methods · 2026Review
- A destination-driven framework for nanoparticle-enabled targeted protein degradation.Acta pharmaceutica Sinica. B · 2026Review
- Mapping and engineering the human cell-cell interactome.Nature biotechnology · 2026Review
- Nanobody-based targeted cancer therapy and immunotherapy: fear not the future.Acta pharmacologica Sinica · 2026Review
- RING finger E3 ubiquitin ligases: novel therapeutic opportunities in melanoma.Cellular & molecular biology letters · 2026Review
- Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026Review
- Targeted shedding of extracellular membrane proteins by induced protease recruitment.bioRxiv : the preprint server for biology · 2026Article
- A cytokine receptor-targeting chimera toolbox for expanding extracellular targeted protein degradation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- PSMA-Targeting Chimeras for Cell-Type-Specific Degradation of Surface Immune Checkpoint Protein PD-L1.JACS Au · 2026Article
- Exploring Novel E3 Ligases and Neosubstrates for Molecular Glue Degraders and Therapeutic Applications in Cancer.Oncology research · 2026Review
- Regulatory roles of E3 ubiquitin ligase RNF128 in inflammatory diseases and tumors.Journal of Cancer · 2026Review
- Chimeras co-targeting antigens and FcγRIIb trigger degradation of extracellular soluble proteins and pathological aggregates.Nature communications · 2025Article
- Recent advances in targeting protein degradation for tumor immunotherapy.Journal of hematology & oncology · 2025Review
- Article
- Structural insights into Wnt/β-catenin signaling regulation by LGR4, R-spondin, and ZNRF3.Nature communications · 2025Article
- A cytokine receptor-targeting chimera (kineTAC) toolbox for expanding extracellular targeted protein degradation.bioRxiv : the preprint server for biology · 2025Article
- Nanoparticle-Mediated Targeted Protein Degradation: An Emerging Therapeutics Technology.Angewandte Chemie (International ed. in English) · 2025Review
- Targeted protein degradation for cancer therapy.Nature reviews. Cancer · 2025Review
- Induced proximity at the cell surface.Nature biotechnology · 2025Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
In recent years, targeted protein degradation (TPD) of plasma membrane proteins by hijacking the ubiquitin proteasome system (UPS) or the lysosomal pathway has emerged as a novel therapeutic avenue in drug development to address and inhibit canonically difficult targets. While TPD strategies have been successful in targeting cell surface receptors, these approaches are limited by the availability of suitable binders to generate heterobifunctional molecules. Here, we present the development of a nanobody (VHH)-based degradation toolbox termed REULR (Receptor Elimination by E3 Ubiquitin Ligase Recruitment). We generated human and mouse cross-reactive nanobodies against five transmembrane PA-TM-RING-type E3 ubiquitin ligases (RNF128, RNF130, RNF167, RNF43, and ZNRF3), covering a broad range and selectivity of tissue expression, with which we characterized the expression in human and mouse cell lines and immune cells (PBMCs). We demonstrate that heterobifunctional REULR molecules can enforce transmembrane E3 ligase interactions with a variety of disease-relevant target receptors (EGFR, EPOR, and PD-1) by induced proximity, resulting in effective membrane clearance of the target receptor at varying levels. In addition, we designed E3 ligase self-degrading molecules, "fratricide" REULRs (RNF128, RNF130, RENF167, RNF43, and ZNRF3), that allow downregulation of one or several E3 ligases from the cell surface and consequently modulate receptor signaling strength. REULR molecules represent a VHH-based modular and versatile "mix and match" targeting strategy for the facile modulation of cell surface proteins by induced proximity to transmembrane PA-TM-RING E3 ligases.
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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.