ArticleNature communications2024
A druggable conformational switch in the c-MYC transactivation domain.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- RAD51AP1-MYC-Sam68 positive transcriptional feedback loop maintains lung cancer stemness.iScience · 2026Article
- Beyond the structure-function paradigm: A comprehensive review of intrinsically disordered proteins.Biochemistry and biophysics reports · 2026Review
- Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Crotonylation impedes c-Myc oncogenic activity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Oncogene c‑Myc: From molecular mechanism to targeted therapy (Review).Molecular medicine reports · 2026Review
- Article
- Exploring the Structural Basis of Cryptic Pocket Formation Driven by Extensive Protein Conformational Changes in Drug Targets.Journal of chemical theory and computation · 2026Article
- Atypical β-strand insertion mediates the noncovalent cross-linking in amyloid aggregates.Nature communications · 2026Article
- New Approach for Targeting Small-Molecule Candidates for Intrinsically Disordered Proteins.Methods and protocols · 2025Article
- Spatially-resolved Photoproximity Profiling of MYC Identifies a MYC-BAF Liability in Cancer Cells.bioRxiv : the preprint server for biology · 2025Article
- Article
- Enforced MYC expression directs a distinct transcriptional state during plasma cell differentiation.Life science alliance · 2025Article
- DIRseq: a method for predicting drug-interacting residues of intrinsically disordered proteins from sequences.bioRxiv : the preprint server for biology · 2025Article
- Ensemble Docking for Intrinsically Disordered Proteins.Journal of chemical information and modeling · 2025Article
- Conformational modulation of intrinsically disordered transactivation domains for cancer therapy.PNAS nexus · 2025Review
- Ensemble docking for intrinsically disordered proteins.bioRxiv : the preprint server for biology · 2025Article
- Exploring the dynamics and interactions of the N-myc transactivation domain through solution nuclear magnetic resonance spectroscopy.The Biochemical journal · 2024Article
- Fibroblast-Specific Protein-Protein Interactions for Myocardial Fibrosis from MetaCore Network.Biomolecules · 2024Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The c-MYC oncogene is activated in over 70% of all human cancers. The intrinsic disorder of the c-MYC transcription factor facilitates molecular interactions that regulate numerous biological pathways, but severely limits efforts to target its function for cancer therapy. Here, we use a reductionist strategy to characterize the dynamic and structural heterogeneity of the c-MYC protein. Using probe-based Molecular Dynamics (MD) simulations and machine learning, we identify a conformational switch in the c-MYC amino-terminal transactivation domain (termed coreMYC) that cycles between a closed, inactive, and an open, active conformation. Using the polyphenol epigallocatechin gallate (EGCG) to modulate the conformational landscape of coreMYC, we show through biophysical and cellular assays that the induction of a closed conformation impedes its interactions with the transformation/transcription domain-associated protein (TRRAP) and the TATA-box binding protein (TBP) which are essential for the transcriptional and oncogenic activities of c-MYC. Together, these findings provide insights into structure-activity relationships of c-MYC, which open avenues towards the development of shape-shifting compounds to target c-MYC as well as other disordered transcription factors for cancer treatment.
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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.