ArticleBiochimica et biophysica acta. General subjects2019
Unexpected implications of STAT3 acetylation revealed by genetic encoding of acetyl-lysine.
Article in Biochimica et biophysica acta. General subjects, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 64 citations in OpenAlex.
- Chemical Profiling and Redox-Target Mapping of Antioxidant Fractions fromPharmaceuticals (Basel, Switzerland) · 2026Article
- Mapping Functionally Relevant Tractable Lysines of Challenging Protein Targets by Covalent Fragment Screening.Chembiochem : a European journal of chemical biology · 2026Article
- Interferon-JAK-STAT Axis in Bone Metabolism.Current osteoporosis reports · 2026Review
- Real-time visualization of STAT activation in live cells using genetically encoded biosensors.Nature chemical biology · 2026Article
- Exploring the mechanism of Platycladi Cacumen in intervening androgenetic alopecia based on network pharmacology, molecular docking, and molecular dynamics simulation.Scientific reports · 2026Article
- STAT3 signaling in cancer: mechanisms and targeting therapeutic.Frontiers in immunology · 2026Review
- Therapeutic Potential ofInternational journal of molecular sciences · 2025Article
- Ultrahigh-Throughput Virtual Screening Strategies against PPI Targets: A Case Study of STAT Inhibitors.Journal of chemical information and modeling · 2025Article
- Allosteric Covalent Inhibitors of the STAT3 Transcription Factor from Virtual Screening.ACS medicinal chemistry letters · 2025Article
- Design and Synthesis of Bis-Chalcones as Curcumin Simplified Analogs and Assessment of Their Antiproliferative Activities Against Human Lung Cancer Cells andPharmaceuticals (Basel, Switzerland) · 2025Article
- Inhibition of histone deacetylase 6 alleviates neuropathic pain via direct regulating post-translation of spinal STAT3 and decreasing downstream C-C Motif Chemokine Ligand 7 synthesis.Journal of neuroinflammation · 2025Article
- The structural influence of the oncogenic driver mutation N642H in the STAT5B SH2 domain.Protein science : a publication of the Protein Society · 2025Article
- Probing the Depths of Molecular Complexity: STAT3 as a Key Architect in Colorectal Cancer Pathogenesis.Current gene therapy · 2025Review
- Discovery of benzethonium chloride as a potent STAT3 inhibitor for the treatment of HNSCC.Frontiers in pharmacology · 2025Article
- Breaking the cancer code: a novel DNA minicircle to disable STAT3 in ovarian cancer cells SKOV3.Frontiers in pharmacology · 2025Article
- Unraveling Stereochemical Structure-Activity Relationships of Sesquiterpene Lactones for Inhibitory Effects on STAT3 Activation.Biomolecules & therapeutics · 2024Article
- 5-AZA Upregulates SOCS3 and PTPN6/SHP1, Inhibiting STAT3 and Potentiating the Effects of AG490 against Primary Effusion Lymphoma Cells.Current issues in molecular biology · 2024Article
- Feasibility of the inhibitor development for cancer: A systematic approach for drug design.PloS one · 2024Article
- UV irradiation remodels the specificity landscape of transcription factors.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Discovery of new STAT3 inhibitors as anticancer agents using ligand-receptor contact fingerprints and docking-augmented machine learning.RSC advances · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The signal transducer and activator of transcription 3 (STAT3) protein is activated by phosphorylation of a specific tyrosine residue (Tyr705) in response to various extracellular signals. STAT3 activity was also found to be regulated by acetylation of Lys685. However, the molecular mechanism by which Lys685 acetylation affects the transcriptional activity of STAT3 remains elusive. By genetically encoding the co-translational incorporation of acetyl-lysine into position Lys685 and co-expression of STAT3 with the Elk receptor tyrosine kinase, we were able to characterize site-specifically acetylated, and simultaneously acetylated and phosphorylated STAT3. We measured the effect of acetylation on the crystal structure, and DNA binding affinity and specificity of Tyr705-phosphorylated and non-phosphorylated STAT3. In addition, we monitored the deacetylation of acetylated Lys685 by reconstituting the mammalian enzymatic deacetylation reaction in live bacteria. Surprisingly, we found that acetylation, per se, had no effect on the crystal structure, and DNA binding affinity or specificity of STAT3, implying that the previously observed acetylation-dependent transcriptional activity of STAT3 involves an additional cellular component. In addition, we discovered that Tyr705-phosphorylation protects Lys685 from deacetylation in bacteria, providing a new possible explanation for the observed correlation between STAT3 activity and Lys685 acetylation.
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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.