ArticlePLoS biology2016
STAT2 Is a Pervasive Cytokine Regulator due to Its Inhibition of STAT1 in Multiple Signaling Pathways.
Article in PLoS biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 64 citations in OpenAlex.
- Quantitative proteomics reveals coordinated changes in the proteome during replicative senescence.Nature communications · 2026Article
- Strong, sustained type I IFN signaling acts cell intrinsically to impair IFNγ responses and cause tuberculosis susceptibility.Cell host & microbe · 2026Article
- Global Proteomic Analysis Reveals Inflammatory Pathway Modulation Associated with miR-146a in LPS-Stimulated Macrophages.International journal of molecular sciences · 2026Article
- STAT2-IRF1-ISG15-Associated Temporal Immune Reprogramming in Macrophages during Aspergillus fumigatus Infection.Current microbiology · 2026Article
- Signal Transduction and Transcription Activator 1 in Pan-Cancer: Prognostic and Immunological Value.Clinical and experimental medicine · 2026Article
- Strong sustained type I IFN signaling acts cell intrinsically to impair IFNγ responses and cause tuberculosis susceptibility.bioRxiv : the preprint server for biology · 2026Article
- STAT2 Promotes Tumor Growth in Colorectal Cancer Independent of Type I IFN Receptor Signaling.Current oncology (Toronto, Ont.) · 2025Article
- IL-4 mediated TAP2 downregulation is a dominant and reversible mechanism of immune evasion and immunotherapy resistance in non-small cell lung cancer.Molecular cancer · 2025Article
- Integrative Multi-PTM Proteomics Reveals Dynamic Global, Redox, Phosphorylation, and Acetylation Regulation in Cytokine-Treated Pancreatic Beta Cells.Molecular & cellular proteomics : MCP · 2024Article
- Transcriptional control of interferon-stimulated genes.The Journal of biological chemistry · 2024Review
- A multi-layered integrative analysis reveals a cholesterol metabolic program in outer radial glia with implications for human brain evolution.Development (Cambridge, England) · 2024Article
- Proximal protein landscapes of the type I interferon signaling cascade reveal negative regulation by PJA2.Nature communications · 2024Article
- Structural mechanism of CRL4-instructed STAT2 degradation via a novel cytomegaloviral DCAF receptor.The EMBO journal · 2023Article
- Generation of porcine PK-15 cells lacking the Ifnar1 or Stat2 gene to optimize the efficiency of viral isolation.PloS one · 2023Article
- MORA and EnsembleTFpredictor: An ensemble approach to reveal functional transcription factor regulatory networks.PloS one · 2023Article
- Downregulation of nuclear STAT2 protein in the spinal dorsal horn is involved in neuropathic pain following chronic constriction injury of the rat sciatic nerve.Frontiers in pharmacology · 2023Article
- The duality of STAT2 mediated type I interferon signaling in the tumor microenvironment and chemoresistance.Cytokine · 2023Review
- Review
- Exposing the Two Contrasting Faces of STAT2 in Inflammation.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2022Review
- Mutations in RNU7-1 Weaken Secondary RNA Structure, Induce MCP-1 and CXCL10 in CSF, and Result in Aicardi-Goutières Syndrome with Severe End-Organ Involvement.Journal of clinical immunology · 2022Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
STAT2 is the quintessential transcription factor for type 1 interferons (IFNs), where it functions as a heterodimer with STAT1. However, the human and murine STAT2-deficient phenotypes suggest important additional and currently unidentified type 1 IFN-independent activities. Here, we show that STAT2 constitutively bound to STAT1, but not STAT3, via a conserved interface. While this interaction was irrelevant for type 1 interferon signaling and STAT1 activation, it precluded the nuclear translocation specifically of STAT1 in response to IFN-γ, interleukin-6 (IL-6), and IL-27. This is explained by the dimerization between activated STAT1 and unphosphorylated STAT2, whereby the semiphosphorylated dimers adopted a conformation incapable of importin-α binding. This, in turn, substantially attenuated cardinal IFN-γ responses, including MHC expression, senescence, and antiparasitic immunity, and shifted the transcriptional output of IL-27 from STAT1 to STAT3. Our results uncover STAT2 as a pervasive cytokine regulator due to its inhibition of STAT1 in multiple signaling pathways and provide an understanding of the type 1 interferon-independent activities of this protein.
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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.