ArticleNature communications2019
Differential PROTAC substrate specificity dictated by orientation of recruited E3 ligase.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 246 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
246 citing papers in PubMed, 507 citations in OpenAlex.
- p38γ and p38δ MAP kinases in inflammation.Biochemical Society transactions · 2026Review
- E3 Ubiquitin Ligases in MASH-Associated Liver Fibrosis: Mechanisms and Therapeutic Opportunities.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- A Versatile DNA-Encoded Library Platform for the Discovery of Highly Cooperative Chemical Inducers of Proximity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cell type-selective targeting by heterobifunctional protein binders via in-cell enrichment.Nature communications · 2026Article
- Proteolysis‑targeting chimeras in oral squamous cell carcinoma: Current evidence, translational challenges and future directions (Review).Molecular medicine reports · 2026Review
- A pharmacological modality to sequester homomeric proteins.Nature chemical biology · 2026Article
- Nanotechnology-Enabled Targeted Protein Degradation: Strategies, Opportunities, and Challenges.Small methods · 2026Review
- PAX3::FOXO1-Targeting PROTAC Induces Myogenic Differentiation of Fusion-Positive Rhabdomyosarcoma Cells.Cancers · 2026Article
- Discovery of SMD-6346: A Potent, Selective, and Orally Active SMARCA2 Degrader for Targeting SMARCA4-Deficient Human Cancers.Journal of medicinal chemistry · 2026Article
- On the Scope of DCAF1-Recruiting PROTACs Degrading Protein Kinases.Journal of medicinal chemistry · 2026Article
- Targeted protein degradation: bridging chemical biology and clinical translation.Acta pharmacologica Sinica · 2026Review
- Structural diversity and chemical space analysis of a PROTAC database using unsupervised machine learning.Scientific reports · 2026Article
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Metastable Protein-Protein Interactions as a Design Principle for PROTACs: Insights from the RIPK1-VHL System.JACS Au · 2026Article
- RNAi-mediated p38δ silencing mitigates anthracycline cardiotoxicity in female mice.American journal of physiology. Heart and circulatory physiology · 2026Article
- Mechanisms and Design Principles of Proteolysis-Targeting Chimeras and Their Emerging Applications.ACS pharmacology & translational science · 2026Review
- Altered residence time as a cause of drug resistance.Current opinion in structural biology · 2026Review
- Phosphatase Signaling as a Therapeutic Strategy in Schizophrenia.International journal of molecular sciences · 2026Review
- A novel proteolysis-targeting chimera strategy targeting multiple immune checkpoints containing ITIMs enhances antitumor immunity.Journal of pharmaceutical analysis · 2026Article
- Targeting the ubiquitin-proteasome system and drug therapy in colorectal cancer.Journal of molecular cell biology · 2026Review
186 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
PROteolysis-TArgeting Chimeras (PROTACs) are hetero-bifunctional molecules that recruit an E3 ubiquitin ligase to a given substrate protein resulting in its targeted degradation. Many potent PROTACs with specificity for dissimilar targets have been developed; however, the factors governing degradation selectivity within closely-related protein families remain elusive. Here, we generate isoform-selective PROTACs for the p38 MAPK family using a single warhead (foretinib) and recruited E3 ligase (von Hippel-Lindau). Based on their distinct linker attachments and lengths, these two PROTACs differentially recruit VHL, resulting in degradation of p38α or p38δ. We characterize the role of ternary complex formation in driving selectivity, showing that it is necessary, but insufficient, for PROTAC-induced substrate ubiquitination. Lastly, we explore the p38δ:PROTAC:VHL complex to explain the different selectivity profiles of these PROTACs. Our work attributes the selective degradation of two closely-related proteins using the same warhead and E3 ligase to heretofore underappreciated aspects of the ternary complex model.
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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.