ArticleJournal of the American Chemical Society2023
Bifunctional Small Molecules That Induce Nuclear Localization and Targeted Transcriptional Regulation.
Article in Journal of the American Chemical Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 47 citations in OpenAlex.
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- TogoPhosTAC as a delivery-ready platform for targeted protein dephosphorylation.Nature communications · 2026Article
- Linkerability of Protein Ligands: Insights From Cocrystal Structures and Implications for DNA-Encoded Libraries.Molecular informatics · 2026Article
- Subcellular localization as a driver of protein function.Nature reviews. Molecular cell biology · 2026Review
- Beyond The Nucleus: Translating Engineered Protein Localization To Chromatin Modifying Enzymes.Current opinion in biomedical engineering · 2026Article
- Activating p53Nature communications · 2026Article
- Mutant p53 protein accumulation is selectively targetable by proximity-inducing drugs.Nature chemical biology · 2026Article
- An epigenetic bifunctional that toggles between transactivation and repression.bioRxiv : the preprint server for biology · 2026Article
- Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026Review
- From Serendipity to Strategy: Rationalizing Molecular Glue Discovery and Proximity-Induced Pharmacology through Chemical Biology.Journal of the American Chemical Society · 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
- Optimizing multifunctional fluorescent ligands for intracellular labeling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Design and Development of DNA Damage Chemical Inducers of Proximity (DD-CIP) for Targeted Cancer Therapy.bioRxiv : the preprint server for biology · 2025Article
- Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Temporal and Spatial Characterization of CUL3ACS chemical biology · 2025Article
- Development and Recent Advances in SLIPT-PM: A Chemogenetic Platform for Manipulating Signaling at the Plasma Membrane.Chembiochem : a European journal of chemical biology · 2025Review
- Lipin1-dependent transcriptional inactivation of SREBPs contributes to selinexor sensitivity in multiple myeloma.Acta pharmacologica Sinica · 2025Article
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6 authors at 1 institution in 1 country.
Funding
Abstract
The aberrant localization of proteins in cells is a key factor in the development of various diseases, including cancer and neurodegenerative disease. To better understand and potentially manipulate protein localization for therapeutic purposes, we engineered bifunctional compounds that bind to proteins in separate cellular compartments. We show these compounds induce nuclear import of cytosolic cargoes, using nuclear-localized BRD4 as a "carrier" for co-import and nuclear trapping of cytosolic proteins. We use this system to calculate kinetic constants for passive diffusion across the nuclear pore and demonstrate single-cell heterogeneity in response to these bifunctional molecules with cells requiring high carrier to cargo expression for complete import. We also observe incorporation of cargo into BRD4-containing condensates. Proteins shown to be substrates for nuclear transport include oncogenic mutant nucleophosmin (NPM1c) and mutant PI3K catalytic subunit alpha (PIK3CA
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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.