ArticleMolecular and cellular biology2010
Impaired binding of 14-3-3 to C-RAF in Noonan syndrome suggests new approaches in diseases with increased Ras signaling.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 126 citations in OpenAlex.
- Article
- Restoring the 14-3-3/CRAF regulatory interaction in Noonan syndrome using molecular glues.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Reporter-based screening identifies RAS-RAF mutations as drivers of resistance to active-state RAS inhibitors in colorectal cancer.Science signaling · 2025Article
- Characterization of multiple binding sites on microtubule associated protein 2c recognized by dimeric and monomeric 14-3-3ζ.The FEBS journal · 2025Article
- 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
- Development of a NanoBRET assay for evaluation of 14-3-3σ molecular glues.SLAS discovery : advancing life sciences R & D · 2024Article
- Regulation of RAF family kinases: new insights from recent structural and biochemical studies.Biochemical Society transactions · 2024Review
- The role of CRAF in cancer progression: from molecular mechanisms to precision therapies.Nature reviews. Cancer · 2024Review
- Exceptional Response to MEK Inhibition in a Patient With RAF1-Mutant Myxofibrosarcoma: Case Report and Mechanistic Overview.JCO precision oncology · 2023Article
- A Systematic Approach to the Discovery of Protein-Protein Interaction Stabilizers.ACS central science · 2023Article
- Article
- De novo and inherited variants in coding and regulatory regions in genetic cardiomyopathies.Human genomics · 2022Article
- Structure of the SHOC2-MRAS-PP1C complex provides insights into RAF activation and Noonan syndrome.Nature structural & molecular biology · 2022Article
- The RASopathies: from pathogenetics to therapeutics.Disease models & mechanisms · 2022Review
- Exploring the Binding Mechanism of a Supramolecular Tweezer CLR01 to 14-3-3σ ProteinFrontiers in chemistry · 2022Article
- Review
- 14-3-3 proteins inactivate DAPK2 by promoting its dimerization and protecting key regulatory phosphosites.Communications biology · 2021Article
- B-Raf autoinhibition in the presence and absence of 14-3-3.Structure (London, England : 1993) · 2021Article
- 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
1 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Ras-RAF-mitogen-activated protein kinase (Ras-RAF-MAPK) pathway is overactive in many cancers and in some developmental disorders. In one of those disorders, namely, Noonan syndrome, nine activating C-RAF mutations cluster around Ser(259), a regulatory site for inhibition by 14-3-3 proteins. We show that these mutations impair binding of 14-3-3 proteins to C-RAF and alter its subcellular localization by promoting Ras-mediated plasma membrane recruitment of C-RAF. By presenting biophysical binding data, the 14-3-3/C-RAFpS(259) crystal structure, and cellular analyses, we indicate a mechanistic link between a well-described human developmental disorder and the impairment of a 14-3-3/target protein interaction. As a broader implication of these findings, modulating the C-RAFSer(259)/14-3-3 protein-protein interaction with a stabilizing small molecule may yield a novel potential approach for treatment of diseases resulting from an overactive Ras-RAF-MAPK pathway.
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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.