ArticleCell chemical biology2020
Polypharmacological Perturbation of the 14-3-3 Adaptor Protein Interactome Stimulates Neurite Outgrowth.
Article in Cell chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Induced ubiquitination of the partially disordered estrogen receptor alpha via a 14-3-3 directed molecular glue-PROTAC.Nature communications · 2026Article
- Understanding the Role of H-Bonds in the Stability of Molecular Glue-Induced Ternary Complexes.Journal of chemical information and modeling · 2026Article
- Article
- From Serendipity to Strategy: Rationalizing Molecular Glue Discovery and Proximity-Induced Pharmacology through Chemical Biology.Journal of the American Chemical Society · 2026Review
- Enantioselective Total Synthesis of (+)-Fusicoccadiene via Photocatalytic Polyene Isomerization.Journal of the American Chemical Society · 2026Article
- Potential 14-3-3 binding sites in sirtuins reveal extended phosphosite-recognition modes.Acta crystallographica. Section F, Structural biology communications · 2026Article
- 14-3-3θ phosphorylation exacerbates alpha-synuclein aggregation and toxicity.Neurobiology of disease · 2025Article
- Fungal toxin fusicoccin enhances plant growth by upregulating 14-3-3 interaction with plasma membrane HScientific reports · 2024Article
- Fragment-Based Interrogation of the 14-3-3/TAZ Protein-Protein Interaction.Biochemistry · 2024Article
- 14-3-3 Protein-Protein Interactions: From Mechanistic Understanding to Their Small-Molecule Stabilization.Chembiochem : a European journal of chemical biology · 2024Review
- Synthesis of (-)-Cotylenol, a 14-3-3 Molecular Glue Component.Journal of the American Chemical Society · 2023Article
- Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3σ/ERα Protein-Protein Interaction from Nonselective Fragments.Journal of the American Chemical Society · 2023Article
- Protein-protein interfaces in molecular glue-induced ternary complexes: classification, characterization, and prediction.RSC chemical biology · 2023Review
- Molecular Glues: Capable Protein-Binding Small Molecules That Can Change Protein-Protein Interactions and Interactomes for the Potential Treatment of Human Cancer and Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme.Beilstein journal of organic chemistry · 2022Article
- Pathways to Parkinson's disease: a spotlight on 14-3-3 proteins.NPJ Parkinson's disease · 2021Review
- The Surprising Story of Fusicoccin: A Wilt-Inducing Phytotoxin, a Tool in Plant Physiology and a 14-3-3-Targeted Drug.Biomolecules · 2021Review
- Targeting the Surface of the Protein 14-3-3 by Ultrasmall (1.5 nm) Gold Nanoparticles Carrying the Specific Peptide CRaf.Chembiochem : a European journal of chemical biology · 2021Article
- 14-3-3 Proteins: Novel Pharmacological Targets in Neurodegenerative Diseases.Trends in pharmacological sciences · 2021Review
- Hierarchized phosphotarget binding by the seven human 14-3-3 isoforms.Nature communications · 2021Article
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Authors and funding
10 authors at 6 institutions in 4 countries.
Funding
Abstract
Targeting protein-protein interactions (PPIs) is a promising approach in the development of drugs for many indications. 14-3-3 proteins are a family of phosphoprotein-binding molecules with critical functions in dozens of cell signaling networks. 14-3-3s are abundant in the central nervous system, and the small molecule fusicoccin-A (FC-A), a tool compound that can be used to manipulate 14-3-3 PPIs, enhances neurite outgrowth in cultured neurons. New semisynthetic FC-A derivatives with improved binding affinity for 14-3-3 complexes have recently been developed. Here, we use a series of screens that identify these compounds as potent inducers of neurite outgrowth through a polypharmacological mechanism. Using proteomics and X-ray crystallography, we discover that these compounds extensively regulate the 14-3-3 interactome by stabilizing specific PPIs, while disrupting others. These results provide new insights into the development of drugs to target 14-3-3 PPIs, a potential therapeutic strategy for CNS diseases.
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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.