ArticleProceedings of the National Academy of Sciences of the United States of America2025
Threonine phosphorylation of STAT1 safeguards gut epithelial integrity and restricts interferon-mediated cytotoxicity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- TNK1 is a targetable JAK-independent driver of STAT signaling and inflammation.Genes & development · 2026Article
- Molecular Target Discovery and Systemic Mechanism Analysis of Teriflunomide for Dry Eye Disease.Current issues in molecular biology · 2026Article
- Magnesium Deficiency Accelerates Gut Aging and Increases Susceptibility to Colitis.Aging cell · 2026Article
- Phosphatases in tumor cell immune escape: a perspective based on the camouflage, coercion, cytoprotection.Frontiers in cell and developmental biology · 2026Review
- Threonine phosphorylation of STAT1 safeguards gut epithelial integrity and restricts interferon-mediated cytotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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Authors and funding
7 authors.
Funding
Abstract
Barrier tissues such as the intestine are constantly challenged by environmental stressors and must adapt to maintain integrity and prevent excessive inflammation. Although traditionally viewed as a proinflammatory effector of interferon (IFN) signaling, STAT1 is shown here to play a protective role in intestinal epithelial cells (IEC) by promoting resilience to damage and restraining IFN-induced cytotoxicity. We identify phosphorylation of threonine 748 (Thr748) on STAT1 as an evolutionarily selected adaptation-highly conserved between humans and mice-that reciprocally regulates IEC integrity and IFN responsiveness. Mice expressing a phospho-deficient T748A Stat1 mutant exhibit severe colitis-induced tissue damage comparable to Stat1-deficient littermates, underscoring the critical role of Thr748 phosphorylation in mediating Stat1-driven protection during intestinal inflammation. Bone marrow transfer experiments further demonstrate that this protective effect is nonhematopoietic. Integrated genomic and transcriptomic analyses reveal that Thr748 phosphorylation modulates STAT1 DNA binding, directly activates the
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