ArticleProceedings of the National Academy of Sciences of the United States of America2015
Mutations in the linker domain affect phospho-STAT3 function and suggest targets for interrupting STAT3 activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 57 citations in OpenAlex.
- A critical role for STAT3 Thr714 phosphorylation in NPM-ALK-driven tumorigenesis.Scientific reports · 2026Article
- Cellular signaling meets bacterial infection: the integrative role of STAT3.Frontiers in cellular and infection microbiology · 2026Review
- Update on Structure and Function of SH2 Domains: Mechanisms and Emerging Targeting Strategies.International journal of molecular sciences · 2025Review
- Decoy-PROTAC for specific degradation of "Undruggable" STAT3 transcription factor.Cell death & disease · 2025Article
- Hyper IgE Syndromes: Understanding, Management, and Future Perspectives: A Narrative Review.Health science reports · 2025Article
- Glucose-Regulated Protein 78, via Releasing β-Catenin from Adherens Junctions, Facilitates Its Interaction with STAT3 in Mediating Retinal Neovascularization.The American journal of pathology · 2024Article
- Enhanced anti-tumor efficacy of S3I-201 in breast cancer mouse model through Wharton jelly- exosome.Cancer cell international · 2024Article
- Article
- Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery.Journal of experimental & clinical cancer research : CR · 2024Review
- Structural determinants of mitochondrial STAT3 targeting and function.Mitochondrial communications · 2024Article
- 4-Octyl itaconate attenuates LPS-induced acute kidney injury by activating Nrf2 and inhibiting STAT3 signaling.Molecular medicine (Cambridge, Mass.) · 2023Article
- Article
- Allosteric regulation in STAT3 interdomains is mediated by a rigid core: SH2 domain regulation by CCD in D170A variant.PLoS computational biology · 2022Article
- STAT3 pathway in cancers: Past, present, and future.MedComm · 2022Review
- Looking for the Holy Grail-Drug Candidates for Glioblastoma Multiforme Chemotherapy.Biomedicines · 2022Review
- A NovelFrontiers in immunology · 2022Article
- Structural exploration with AlphaFold2-generated STAT3α structure reveals selective elements in STAT3α-GRIM-19 interactions involved in negative regulation.Scientific reports · 2021Article
- Article
- The Dual Role of STAT1 in Ovarian Cancer: Insight Into Molecular Mechanisms and Application Potentials.Frontiers in cell and developmental biology · 2021Review
- Stat2 stability regulation: an intersection between immunity and carcinogenesis.Experimental & molecular medicine · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Crystallography of the cores of phosphotyrosine-activated dimers of STAT1 (132-713) and STAT3 (127-722) bound to a similar double-stranded deoxyoligonucleotide established the domain structure of the STATs and the structural basis for activation through tyrosine phosphorylation and dimerization. We reported earlier that mutants in the linker domain of STAT1 that connect the DNA-binding domain and SH2 domain can prevent transcriptional activation. Because of the pervasive importance of persistently activated STAT3 in many human cancers and the difficulty of finding useful drug candidates aimed at disrupting the pY interchange in active STAT3 dimers, we have examined effects of an array of mutants in the STAT3 linker domain. We have found several STAT3 linker domain mutants to have profound effects of inhibiting STAT3 transcriptional activation. From these results, we propose (i) there is definite functional interaction of the linker both with the DNA binding domain and with the SH2 domain, and (ii) these putative contacts provide potential new targets for small molecule-induced pSTAT3 inhibition.
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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.