ArticleScience (New York, N.Y.)2024
Relocalizing transcriptional kinases to activate apoptosis.
Article in Science (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- A Versatile DNA-Encoded Library Platform for the Discovery of Highly Cooperative Chemical Inducers of Proximity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A bivalent molecular glue linking lysine acetyltransferases to oncogene-induced cell death.Cell · 2026Article
- A pharmacological modality to sequester homomeric proteins.Nature chemical biology · 2026Article
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- Discovery of Noninhibitory Macrocyclic Ligands for Protein Tyrosine Phosphatase 1B Using a Function-Based, Iterative Screening Strategy.Journal of the American Chemical Society · 2026Article
- Proteomics-Driven Strategies for Proximity-Inducing Drug Discovery.Angewandte Chemie (International ed. in English) · 2026Review
- Targeted Transcriptional Repression by Induced Proximity.ACS central science · 2026Article
- Article
- Technologies to measure and modulate protein subcellular localization.Nature reviews. Molecular cell biology · 2026Review
- Induced-proximity therapeutics for targeted protein and RNA degradation: An organic chemistry Perspective-A review.Current research in structural biology · 2026Review
- Activating p53Nature communications · 2026Article
- Rewiring Oncogenic Transcriptional Complexes with Domain-ALTeration Chimeras (DALTACs) in Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
- An epigenetic bifunctional that toggles between transactivation and repression.bioRxiv : the preprint server for biology · 2026Article
- Mechanisms of resistance to bruton's tyrosine kinase inhibitors: synergistic effects of tumor microenvironment regulation and signaling pathways.Annals of hematology · 2026Review
- From Serendipity to Strategy: Rationalizing Molecular Glue Discovery and Proximity-Induced Pharmacology through Chemical Biology.Journal of the American Chemical Society · 2026Review
- CDK12 and CDK13 in oncology: from RNA regulation to therapeutic targeting.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Engineered anchoring aptamers induce relocalization and functional inactivation of transcription factors.Science advances · 2026Article
- Reporter Gene Assay for Monitoring BCL6 Reactivation.Methods in molecular biology (Clifton, N.J.) · 2026Article
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15 authors.
Funding
Abstract
Kinases are critical regulators of cellular function that are commonly implicated in the mechanisms underlying disease. Most drugs that target kinases are molecules that inhibit their catalytic activity, but here we used chemically induced proximity to convert kinase inhibitors into activators of therapeutic genes. We synthesized bivalent molecules that link ligands of the transcription factor B cell lymphoma 6 (BCL6) to inhibitors of cyclin-dependent kinases (CDKs). These molecules relocalized CDK9 to BCL6-bound DNA and directed phosphorylation of RNA polymerase II. The resulting expression of pro-apoptotic, BCL6-target genes caused killing of diffuse large B cell lymphoma cells and specific ablation of the BCL6-regulated germinal center response. Genomics and proteomics corroborated a gain-of-function mechanism in which global kinase activity was not inhibited but rather redirected. Thus, kinase inhibitors can be used to context-specifically activate transcription.
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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.