Affinage

STAT1

Signal transducer and activator of transcription 1-alpha/beta · UniProt P42224

Length
750 aa
Mass
87.3 kDa
Annotated
2026-06-10
100 papers in source corpus 47 papers cited in narrative 46 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STAT1 is a latent cytoplasmic transcription factor that converts cytokine receptor engagement into interferon-stimulated gene (ISG) transcription, governing antiviral defense, cell-cycle arrest, autophagy, apoptosis, and inflammatory gene programs (PMID:7690989, PMID:1502203, PMID:1502204). In response to IFN-gamma, JAK1 phosphorylates STAT1 on a single residue, Tyr701, which is required for homodimer formation, nuclear translocation, DNA binding, and gene activation; the C-terminal transactivation domain is independently essential for transcription (PMID:7690989, PMID:8114747). Dimerization occurs through reciprocal SH2-domain recognition of the partner's phosphotyrosine, and only the phosphorylated dimer binds DNA (PMID:7510216), while in the IFN-alpha response phosphorylated STAT1 assembles with STAT2 and a DNA-binding subunit into the ISGF3 complex that drives ISG expression (PMID:1502203, PMID:1502204, PMID:8197134). Crystallographic and biophysical analysis show that unphosphorylated STAT1 is already dimeric through N-domain contacts and interconverts between antiparallel and parallel orientations, and that the SH2 domain docks onto the IFN-gamma receptor phosphopeptide (PMID:15780933). Nuclear accumulation proceeds in two steps—importin-dependent import followed by DNA-binding-mediated retention—and recycling requires tyrosine dephosphorylation and CRM1-dependent export, with continuous nucleocytoplasmic cycling sustained by ongoing kinase activity (PMID:12923054, PMID:12915721). A dense post-translational code tunes this cycle: Ser727 phosphorylation by PKCdelta links STAT1 to DNA-damage-induced apoptosis (PMID:15322115); acetylation at Lys410/413 by CBP (reversed by HDAC3) recruits the phosphatase TC45 to drive latency and redirects STAT1 to antagonize NF-kappaB p65 (PMID:16481475, PMID:19171783); K63-linked ubiquitination by RNF220 at Lys110 and by NKLAM promotes JAK1 association and DNA binding (PMID:32814877, PMID:27570112); linear ubiquitination by LUBAC at Lys511/Lys652, removed by OTULIN, restrains receptor engagement (PMID:32123171); and PARP14-mediated ADP-ribosylation, antagonized by PARP9, suppresses phosphorylation (PMID:27796300). Beyond canonical JAK signaling, STAT1 is activated by Syk downstream of RIG-I/MAVS during viral infection (PMID:33472080) and by IKK-phosphorylation at Thr748, an IFN-independent inflammatory switch (PMID:38621137). As a transcription factor STAT1 directly activates targets including NAMPT, S1PR1, and HK2 and represses ULK1, FOXM1, and HIF1A, thereby controlling macrophage metabolism, autophagy, and angiogenesis (PMID:33976173, PMID:28011640, PMID:36300763, PMID:32006593), and it acts independently of IFN receptors as a cytoplasmic attenuator of Runx2 in osteoblasts and as a downstream effector of PDGFRbeta-driven autoinflammation (PMID:15546140, PMID:28924035). Gain-of-function disease variants act by elevating total STAT1 protein and thus peak phospho-STAT1 rather than by impairing dephosphorylation (PMID:31354696).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1992 High

    Established that STAT1 is a physical component of a cytokine-activated nuclear transcription complex, defining it as a signal-dependent transcription factor rather than a constitutive regulator.

    Evidence Protein purification, peptide sequencing, and cDNA cloning of the ISGF-3 complex activated by IFN-alpha

    PMID:1502203 PMID:1502204

    Open questions at the time
    • Did not define the activating modification
    • Stoichiometry and assembly order of ISGF3 subunits unresolved at this stage
  2. 1993 High

    Pinpointed the single activating event—Tyr701 phosphorylation—and separated activation from transcriptional output by showing the C-terminal transactivation domain is independently required.

    Evidence Site-directed mutagenesis, phosphorylation mapping, and reporter assays comparing full-length and C-terminally truncated isoforms in IFN-gamma response

    PMID:7690989

    Open questions at the time
    • Did not identify the kinase responsible
    • Dimerization mechanism not yet defined
  3. 1994 High

    Defined the dimerization mechanism and upstream kinase, showing phospho-Tyr701 drives SH2-mediated homodimer formation and that JAK1 is the kinase required for STAT1 activation by both type I and II IFNs.

    Evidence Dissociation/reassociation biochemistry with SH2 mutants and gel-shift assays; JAK1-deficient mutant cell complementation

    PMID:7510216 PMID:8114747 PMID:8197134

    Open questions at the time
    • Structural basis of the SH2-phosphopeptide docking not yet resolved
    • Did not address non-IFN receptor inputs
  4. 1994 Medium

    Showed STAT1 activation is not restricted to interferons, extending it to growth hormone and GPCR (angiotensin II/AT1A) signaling and broadening its physiological scope.

    Evidence In vivo GH liver model and AT1A receptor activation with nuclear fractionation, EMSA, and tyrosine kinase inhibitor studies

    PMID:7510676 PMID:7527386

    Open questions at the time
    • Kinases coupling GH/GPCR receptors to STAT1 not fully defined
    • Physiological gene targets in these contexts not mapped
  5. 1998 Medium

    Identified negative regulation and cooperative DNA recognition, with PIAS1 blocking activated STAT1 DNA binding and N-domain contacts driving heterotetramer formation on tandem GAS/ISRE sites.

    Evidence Reciprocal co-IP, EMSA with Tyr701 and N-terminal deletion mutants; caspase cleavage abolishing signaling during apoptosis

    PMID:9535846 PMID:9724754 PMID:9865492

    Open questions at the time
    • Whether PIAS1 acts catalytically or stoichiometrically not defined
    • In vivo significance of heterotetramers not established
  6. 2003 High

    Resolved the nuclear trafficking cycle: import plus DNA-binding-mediated retention, dephosphorylation-dependent CRM1 export, and energy-independent diffusion to the nuclear pore sustained by continuous kinase activity.

    Evidence Microinjection of recombinant STAT1, FRAP/FLIP live imaging of STAT1-GFP, kinase/phosphatase inhibitors, and domain mapping

    PMID:11350940 PMID:12915721 PMID:12923054

    Open questions at the time
    • Identity of the nuclear phosphatase not yet established here
    • Import receptor identity addressed only later
  7. 2005 High

    Provided the structural model of STAT1, showing unphosphorylated dimers held by N-domain contacts and interconverting antiparallel/parallel conformations with the SH2 domain docked on the IFN-gamma receptor peptide.

    Evidence X-ray crystallography at 3.0 A with analytical ultracentrifugation, light scattering, and co-IP

    PMID:15780933

    Open questions at the time
    • Structure of the phosphorylated DNA-bound dimer not in this study
    • Full-length C-terminal transactivation domain not resolved
  8. 2005 Medium

    Revealed an IFN-independent cytoplasmic role, with STAT1 attenuating Runx2 to restrain osteoblast differentiation and bone mass.

    Evidence Stat1-knockout mice with osteoblast differentiation and Runx2 nuclear translocation assays

    PMID:15546140

    Open questions at the time
    • Molecular basis of cytoplasmic Runx2 sequestration not defined
    • Whether STAT1 modifications regulate this function unknown
  9. 2006 Medium

    Opened the post-translational regulatory layer by identifying acetylation (Lys410/413, CBP-dependent) as a modification that reroutes STAT1 to antagonize NF-kappaB p65 and SUMOylation at Lys703 as a modest DNA-binding/retention modulator.

    Evidence Acetylation- and SUMO-site mutants, co-IP, HAT/HDAC modulation, and in vitro SUMOylation with complementation in STAT1-/- cells

    PMID:16481475 PMID:16857984

    Open questions at the time
    • In vivo significance of K703 SUMOylation appears limited
    • Crosstalk between acetylation and phosphorylation not yet defined here
  10. 2009 High

    Defined a phosphorylation-acetylation switch, showing CBP acetylation recruits the phosphatase TC45 to dephosphorylate STAT1 and impose latency, reversed by HDAC3.

    Evidence Acetylation/phosphorylation mutants, HAT/HDAC modulation, co-IP, and reporter assays reconstituting the switch

    PMID:19171783

    Open questions at the time
    • Whether the switch operates at all receptors not tested
    • Spatial coordination of TC45 recruitment unresolved
  11. 2010 Medium

    Connected STAT1 to cell-cycle control via direct cyclin D1/CDK4 binding and Ser727-dependent proteasomal cyclin D1 degradation, mediating IFN-gamma-induced arrest.

    Evidence Co-IP, proteasome inhibition, and Ser727/Tyr701 mutant analysis in STAT1-deficient cells

    PMID:21084836

    Open questions at the time
    • Whether degradation is direct or transcriptionally mediated not resolved
    • Single lab
  12. 2014 High

    Showed STAT1 governs inflammatory output beyond ISG transcription by promoting HMGB1 NLS hyperacetylation and nucleocytoplasmic translocation.

    Evidence Mass spectrometry acetylation mapping, JAK inhibition, STAT1 knockout, and subcellular fractionation

    PMID:24469805

    Open questions at the time
    • Acetyltransferase linking STAT1 to HMGB1 not identified
    • Direct vs indirect mechanism unresolved
  13. 2016 High

    Established ubiquitin and ADP-ribosylation control of STAT1, with NKLAM K63-ubiquitination required for DNA binding, PARP14 ADP-ribosylation suppressing phosphorylation (antagonized by PARP9), and STAT1 directly driving NAMPT for macrophage metabolic reprogramming.

    Evidence K63-specific ubiquitination assays in NKLAM-KO macrophages; ADP-ribosylation with PARP9/14 silencing and site mutagenesis; ChIP with NRE1 disruption mouse

    PMID:27570112 PMID:27796300 PMID:33976173

    Open questions at the time
    • How K63 ubiquitination mechanistically enables DNA binding unclear
    • Interplay among competing modifications not integrated
  14. 2016 High

    Identified STAT1 as a transcriptional repressor of autophagy via direct suppression of ULK1, integrating STAT1 with mTOR-regulated autophagic flux.

    Evidence ChIP, promoter reporter mutagenesis, and STAT1-deficient cells and mice with autophagic flux measurement

    PMID:28011640

    Open questions at the time
    • Whether ULK1 repression requires Tyr701 vs Ser727 not defined
    • Cofactors at the ULK1 promoter unknown
  15. 2017 High

    Defined STAT1-IRF1 enhancer co-occupancy as a determinant of ISG responsiveness and revealed an IFN-receptor-independent role for STAT1 downstream of PDGFRbeta in autoinflammation and tissue wasting.

    Evidence ChIP-seq of STAT1/IRF1 across cell types; genetic epistasis of Stat1-/- with Pdgfrb gain-of-function and Ifnar1/Ifngr1 knockout crosses

    PMID:28274199 PMID:28924035

    Open questions at the time
    • How PDGFRbeta activates STAT1 without IFN receptors not defined
    • Determinants of STAT1/IRF1 co-binding selectivity unresolved
  16. 2019 Medium

    Expanded regulators and targets: PHLPP1 dephosphorylates nuclear Ser727 to limit promoter residency, IRF1 sustains STAT1 Tyr701 phosphorylation via an indirect feedback loop, and STAT1 represses FOXM1 to sensitize tumor cells.

    Evidence PHLPP1-KO mice with ChIP; IRF1-KO/complementation with GAS reporters; ChIP and luciferase at the FOXM1 promoter

    PMID:29893425 PMID:30782607 PMID:31408005

    Open questions at the time
    • Cytokine mediating IRF1-driven STAT1 activation not identified
    • PHLPP1 substrate selectivity within the nucleus not fully mapped
  17. 2019 Medium

    Reframed the basis of STAT1 gain-of-function disease, showing elevated total STAT1 protein—not impaired dephosphorylation—drives high peak phospho-STAT1.

    Evidence Flow cytometry, immunoblot, qRT-PCR, cycloheximide chase, and ruxolitinib dephosphorylation kinetics in patient PBMCs

    PMID:31354696

    Open questions at the time
    • Mechanism elevating STAT1 mRNA in patients not defined
    • Single patient-cell study
  18. 2020 High

    Resolved layered ubiquitin and conformational control of STAT1 activation, with LUBAC linear ubiquitination (OTULIN-reversed) restraining receptor binding, RNF220 K63-ubiquitination at Lys110 promoting JAK1 association, and IKK-epsilon phosphorylation of STAT2 disrupting the inactive U-STAT1-U-STAT2 dimer to enable ISGF3 assembly.

    Evidence Linear/K63 ubiquitination assays with site mutagenesis, DUB/E3 manipulation, receptor-binding and JAK1 interaction assays, EM structure, and T403A/HOIL-1L mouse models

    PMID:32123171 PMID:32759968 PMID:32814877

    Open questions at the time
    • How competing ubiquitin marks are temporally coordinated unresolved
    • Stoichiometry of the U-STAT1-U-STAT2 pool unknown
  19. 2020 Medium

    Extended STAT1's transcriptional repertoire to angiogenesis and signaling regulation, repressing HIF1A and activating S1PR1, with additional oxidative S-glutathionylation reported to hyperactivate STAT1.

    Evidence ChIP/EMSA/reporter assays at HIF1A and S1PR1 promoters with knockdown/overexpression; S-glutathionylation assay in BV2 microglia

    PMID:31121156 PMID:32006593 PMID:36300763

    Open questions at the time
    • S-glutathionylation site not mapped or validated by mutagenesis (Low-confidence)
    • Context-dependence of activation vs repression at different promoters unresolved
  20. 2021 High

    Identified cytokine-independent activation and protein-level stabilization of STAT1, with Syk phosphorylating Tyr701 downstream of RIG-I/MAVS during influenza and CCT6A protecting STAT1 from proteasomal degradation to drive HK2-dependent glycolysis.

    Evidence Syk deletion and STAT1-Y701F knockin mice; co-IP/MS, ChIP, and ubiquitination assays with CCT6A silencing

    PMID:33472080 PMID:38750462

    Open questions at the time
    • Whether Syk acts at the receptor or in the cytosol not fully defined
    • CCT6A finding from a single lab
  21. 2022 Medium

    Revealed cytoplasmic gating of STAT1 nuclear entry, with ADAP competing against importin alpha5 for STAT1 binding to restrain nuclear translocation and FcgammaR-driven phagocytosis.

    Evidence Co-IP of ADAP-STAT1-importin alpha5, ADAP-/- mice, nuclear translocation and FcgammaR expression assays, and pharmacological STAT1 inhibition

    PMID:35637282

    Open questions at the time
    • Whether ADAP regulation is modification-dependent unknown
    • Single lab
  22. 2023 Medium

    Connected STAT1 to transcriptional machinery recruitment and additional disease contexts, with DHX9 bridging STAT1 to RNA Pol II at ISG promoters, MST4 phosphorylating STAT1 for M1 polarization, and STAT1 repressing microglial Ulk1 in synucleinopathy.

    Evidence Co-IP and ChIP with conditional DHX9/STAT1 double-KO mice; co-IP/MS and Mst4 conditional KO; luciferase, KO/KD, and conditional microglial Stat1-KO with TLR4 dependency

    PMID:36735791 PMID:37833401 PMID:39462396

    Open questions at the time
    • Direct vs scaffold role of DHX9 in Pol II loading not separated
    • Each finding from a single lab
  23. 2024 High

    Defined an IFN-independent inflammatory phosphorylation switch and further metabolic/disease roles, with IKK phosphorylating STAT1 at Thr748 to bias macrophages toward inflammation and STAT1 partnering with PRMT6 to drive ACSL1-dependent ferroptosis.

    Evidence T748A knockin mice with IKK kinase assay and LPS lethality model; co-IP and ChIP with PRMT6-/- mice and lipidomics

    PMID:38621137 PMID:39134684

    Open questions at the time
    • How Thr748 phosphorylation mechanistically suppresses IFN output unresolved
    • PRMT6-STAT1 finding from a single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dense array of competing post-translational modifications, cytoplasmic gating factors, and alternative kinases is integrated to set STAT1 activity in a given cell and stimulus remains unresolved.
  • No unified quantitative model of PTM crosstalk on STAT1
  • Stimulus- and cell-type-specific selection between JAK1, Syk, IKK, MST4, and PKCdelta inputs not defined
  • Determinants directing STAT1 to activate vs repress specific target promoters unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 5 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 4 GO:0005654 nucleoplasm 2
Pathway
R-HSA-168256 Immune System 6 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-162582 Signal Transduction 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-9612973 Autophagy 2 R-HSA-1640170 Cell Cycle 1
Partners
CBPDHX9IMPORTIN ALPHA5JAK1PARP14PIAS1RNF220STAT2
Complex memberships
ISGF3

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 STAT1 (Stat91) is phosphorylated on a single tyrosine residue (Tyr701) in response to IFN-gamma, and phosphorylation of Tyr701 is required for nuclear translocation, DNA binding, and gene activation. The differentially spliced isoform Stat84, lacking the 38 C-terminal amino acids, was phosphorylated and translocated but did not activate transcription, demonstrating that the C-terminal transactivation domain is essential. Site-directed mutagenesis, phosphorylation mapping, nuclear translocation assay, transcriptional reporter assay Science High 7690989
1992 STAT1 (91-kDa and 84-kDa proteins) are components of the multiprotein transcription factor ISGF-3, which is cytoplasmically activated by IFN-alpha and translocates to the nucleus to drive interferon-stimulated gene expression. ISGF-3 also contains a 113-kDa protein (STAT2) and a 48-kDa DNA-binding subunit. Protein purification, peptide sequencing, cDNA cloning, antibody validation (immunoprecipitation) Proceedings of the National Academy of Sciences of the United States of America High 1502203 1502204
1994 Inactive STAT1 (Stat91) is a monomer in the cytoplasm of unstimulated cells; IFN-gamma-induced Tyr701 phosphorylation drives formation of a stable homodimer. Only the phosphorylated dimer binds specific DNA sequences to activate transcription. Dimerization is mediated through SH2 domain recognition of the phosphotyrosyl peptide on the partner molecule. Dissociation/reassociation biochemical assays, SH2 mutant analysis, gel-shift DNA-binding assay, analytical biochemistry Cell High 7510216
1994 ISGF-3 formation requires phosphorylated Stat91 (STAT1); mutations blocking Tyr701 phosphorylation of the 91-kDa protein prevent ISGF-3 assembly. Stat113 (STAT2) is phosphorylated independently of Stat91/84, but phosphorylated STAT2 alone translocates to the nucleus much less efficiently in the absence of phosphorylated Stat91/84. Cell lines lacking Stat91/84, site-directed mutagenesis, co-immunoprecipitation, nuclear fractionation Proceedings of the National Academy of Sciences of the United States of America High 8197134
1994 JAK1 kinase is required for tyrosine phosphorylation of STAT1 (84- and 91-kDa) and STAT2 in response to both IFN-alpha/beta and IFN-gamma signaling. Mutant HeLa cells deficient in JAK1 fail to phosphorylate STAT1 on tyrosine and fail to mount a biological IFN response. Mutant cell line complementation analysis, immunoprecipitation, tyrosine phosphorylation assays, cell fusion analysis Molecular and cellular biology High 8114747
1998 PIAS1 specifically inhibits STAT1-mediated gene activation by blocking the DNA-binding activity of activated STAT1. PIAS1 physically associates with phosphorylated STAT1 (requiring Tyr701 phosphorylation) but not with STAT2 or STAT3. Other PIAS family members do not bind STAT1. Co-immunoprecipitation, electrophoretic mobility shift assay (DNA-binding), transcriptional reporter assay, Tyr701 mutant analysis Proceedings of the National Academy of Sciences of the United States of America High 9724754
1998 STAT1 is cleaved by a caspase during apoptosis (induced by double-stranded RNA and other apoptotic stimuli). The cleavage product is no longer able to mediate interferon-activated signal transduction. In vitro caspase cleavage assay, IFN signaling functional assay, apoptosis induction The Journal of biological chemistry Medium 9535846
2003 Nuclear accumulation of phosphorylated STAT1 involves two separate steps: nuclear import and nuclear retention (mediated by nonspecific DNA binding of activated STAT1). Tyrosine dephosphorylation of STAT1 is required for nuclear export; DNA binding protects STAT1 from dephosphorylation in a sequence-specific manner. STAT1 undergoes continuous nucleocytoplasmic cycling sustained by kinase activity. Microinjection of recombinant STAT1, kinase/phosphatase inhibitor treatment, nuclear accumulation mutant characterization, antibody microinjection Genes & development High 12923054
2003 STAT1 translocation from the plasma membrane to the nuclear pore occurs by energy-independent diffusion (random walk), independent of the actin cytoskeleton or microtubules. Nuclear STAT1-GFP shows high mobility consistent with rapid association/dissociation with DNA and/or protein complexes. FRAP, FLIP, live-cell fluorescence microscopy with STAT1-GFP fusion protein, cytoskeletal disruption The EMBO journal High 11350940
2003 Nuclear import and export signals of STAT1 reside within its DNA-binding domain. After phosphorylation and dimerization, STAT1's nuclear localization signal is revealed. Upon dephosphorylation and DNA dissociation in the nucleus, a CRM1-dependent nuclear export signal becomes accessible, mediating recycling to the cytoplasm. Domain mapping, export inhibitor studies, mutant STAT1 analysis Science's STKE Medium 12915721
2005 Crystal structure of unphosphorylated STAT1 (residues 1-683) complexed with an IFNgamma receptor phosphopeptide determined at 3.0 Å resolution. Unphosphorylated STAT1 is predominantly dimeric, mediated by N-domain (residues 1-123) interactions. Two interconvertible orientations of the core fragment are observed ('antiparallel' and 'parallel'), depending on SH2 domain orientation. The SH2 domain interaction with the IFNgamma receptor docking site is structurally resolved. X-ray crystallography (3.0 Å), static light scattering, analytical ultracentrifugation, co-immunoprecipitation Molecular cell High 15780933
2005 STAT1 functions as a cytoplasmic attenuator of Runx2 (a key transcription factor for osteoblast differentiation) independently of IFN signaling. Loss of Stat1 in mice leads to excessive Runx2 activation and increased osteoblast differentiation, resulting in increased bone mass. Stat1-knockout mice, osteoblast differentiation assays, Runx2 nuclear translocation analysis Journal of cellular biochemistry Medium 15546140
2006 STAT1 is an acetylated protein; acetylation is regulated by the balance between CBP (HAT) and HDACs. Both HDAC inhibitors and IFN-alpha induce STAT1 acetylation at Lys410 and Lys413. Only acetylated STAT1 interacts with NF-kappaB p65, reducing p65 DNA binding, nuclear localization, and expression of anti-apoptotic NF-kappaB target genes. STAT1 acetylation mutants (Lys410/413), co-immunoprecipitation, HDAC/HAT inhibitor treatment, reporter gene assay, DNA-binding assay Genes & development High 16481475
2009 A phosphorylation-acetylation switch regulates STAT1 signaling: CBP-mediated acetylation of STAT1 counteracts IFN-induced STAT1 phosphorylation, nuclear translocation, DNA binding, and target gene expression. Acetylation of STAT1 induces binding of T-cell protein tyrosine phosphatase (TC45/TCP45), which catalyzes dephosphorylation of STAT1 and promotes latency. HDAC3 removes the acetyl group, allowing re-phosphorylation. Biochemical assays, STAT1 acetylation/phosphorylation mutants, HAT/HDAC activity modulation, co-immunoprecipitation, transcriptional reporter assay Genes & development High 19171783
2010 STAT1 directly interacts with cyclin D1 and CDK4 (G1 cell cycle regulatory proteins). IFN-gamma treatment reduces cyclin D1 protein levels via the proteasome pathway in a manner requiring STAT1 Ser727 (not Tyr701). This interaction and proteasomal degradation of cyclin D1 mediate cell cycle arrest, correlating with decreased pRb, cyclin E and increased p27 and p21. Co-immunoprecipitation, proteasome inhibitor treatment, STAT1 mutant analysis (Ser727, Tyr701), STAT1-deficient cell lines Cell cycle Medium 21084836
1994 Growth hormone (GH) rapidly induces tyrosine phosphorylation and nuclear translocation of STAT91 (STAT1) in vivo in rat liver. Activated STAT1 in the nucleus acquires DNA-binding activity toward a c-sis-inducible element (SIE) from the c-fos promoter, establishing that GH activates the STAT1 pathway. Western blotting of nuclear extracts, anti-phosphotyrosine immunoprecipitation, gel-mobility shift assay, in vivo GH treatment model The Journal of biological chemistry Medium 7510676
1994 Angiotensin II acting through the AT1A receptor (a G-protein-coupled receptor) activates STAT1 (Stat91) or a related protein, inducing tyrosine phosphorylation and nuclear translocation of STAT1 and stimulating SIE-dependent DNA-binding activity. This response is sensitive to tyrosine kinase inhibition (genistein) and independent of new protein synthesis. Electrophoretic mobility shift assay (EMSA), subcellular fractionation, immunoprecipitation, tyrosine kinase inhibitor studies The Journal of biological chemistry Medium 7527386
2004 PKCdelta activates STAT1 via phosphorylation of Ser727 in response to DNA damage (etoposide). STAT1 associates with PKCdelta, and nuclear co-localization of PKCdelta and STAT1 is required for PKCdelta-mediated apoptosis. STAT1beta lacking Ser727 does not support PKCdelta-induced apoptosis in STAT1-deficient cells. Co-immunoprecipitation, PKCdelta inhibition/depletion, STAT1 Ser727 mutant, STAT1-deficient cell line (U3A) complementation, transcriptional reporter assay, nuclear localization mutants The Journal of biological chemistry Medium 15322115
2006 STAT1 can be SUMOylated in vitro at Lys703 within the consensus SUMO site (702-IKTE-705). Mutation of K703 (K703R) in STAT1 enhances DNA binding and nuclear retention in STAT1-deficient MEFs, with modest effects on transcription and antiviral activity. Mutation of E705 (E705A) does not alter STAT1 activity, suggesting SUMO modification at Lys703 has limited physiological significance in vivo. In vitro SUMOylation assay, STAT1 mutant expression in STAT1-/- MEFs and macrophages, DNA-binding assay, nuclear retention assay Blood Medium 16857984
2014 JAK/STAT1 pathway activation promotes HMGB1 hyperacetylation at its two nuclear localization sequences (NLS) and induces HMGB1 translocation from nucleus to cytoplasm. Pharmacological inhibition or genetic deletion of STAT1 abrogates LPS- or type I IFN-induced HMGB1 NLS acetylation and nuclear translocation. Mass spectrometry acetylation mapping, JAK inhibitor treatment, STAT1 genetic knockout, subcellular fractionation Proceedings of the National Academy of Sciences of the United States of America High 24469805
2016 PARP14 mediates ADP-ribosylation of STAT1, which is suppressed by PARP9. ADP-ribosylation of STAT1 by PARP14 reduces STAT1 phosphorylation; mutations at ADP-ribosylation sites lead to increased STAT1 phosphorylation. PARP9 and PARP14 cross-regulate macrophage activation via this STAT1 ADP-ribosylation mechanism. Global proteomics, ADP-ribosylation assay, PARP9/14 silencing, phosphorylation analysis, site-directed mutagenesis of ADP-ribosylation sites Nature communications High 27796300
2020 STAT1 undergoes linear ubiquitination at Lys511 and Lys652 by the LUBAC complex (via HOIP), which inhibits STAT1 binding to the IFN receptor IFNAR2, restricting STAT1 activation and maintaining type-I IFN signaling homeostasis. The deubiquitinase OTULIN removes linear ubiquitin from STAT1 upon IFN stimulation to facilitate activation. Viruses induce HOIP expression via NF-κB, thereby increasing STAT1 linear ubiquitination and suppressing antiviral IFN responses. Linear ubiquitination assay in intact cells, site-directed mutagenesis (K511, K652), OTULIN/HOIP knockdown and overexpression, IFNAR2 binding assay, HOIL-1L heterozygous mouse model Nature communications High 32123171
2020 RNF220 E3 ubiquitin ligase mediates K63-linked polyubiquitination of STAT1 at residue Lys110, which promotes the interaction between STAT1 and JAK1, thereby enhancing STAT1 phosphorylation and activation. RNF220 deficiency impairs IFN signaling and ISG expression. Co-immunoprecipitation, K63-specific ubiquitination assay, site-directed mutagenesis (K110), RNF220 knockout cells and mice, JAK1-STAT1 interaction assay Cell death and differentiation High 32814877
2021 Syk tyrosine kinase, acting downstream of RIG-I/MAVS signaling, directly phosphorylates STAT1 at Tyr701 at the early stage of influenza A virus infection independently of cytokines and JAKs. Syk deletion attenuates STAT1 phosphorylation and ISG expression; STAT1-Y701F knockin mice have suppressed antiviral response. Syk deletion (in vitro and in vivo), STAT1-Y701F knockin mice, RIG-I/MAVS pathway analysis, tyrosine phosphorylation assays Cell reports High 33472080
1998 Stat1-2 heterodimers form heterotetramers on tandem GAS sites through protein-protein interactions mediated by N-terminal regions of both Stat1 and Stat2. Deletion of 40 N-terminal amino acids from Stat1 abolishes heterotetramer formation without affecting heterodimer formation. ISGF3 also shows cooperative binding to tandem ISREs via N-terminal domain interactions. EMSA with tandem DNA elements, N-terminal deletion mutants, cooperative binding assays Biochimie Medium 9865492
2019 PHLPP1 phosphatase dephosphorylates STAT1 at Ser727 in the nucleus, inhibiting STAT1 transcriptional activity, reducing its promoter residency, and decreasing expression of target genes involved in innate immunity. This function requires a bipartite nuclear localization signal in PHLPP1's N-terminal extension. PHLPP1 gene deletion (knockout mice), phosphorylation assays, chromatin immunoprecipitation (promoter occupancy), gene expression analysis, nuclear localization signal mapping eLife High 31408005
2016 NKLAM E3 ubiquitin ligase mediates K63-linked ubiquitination of STAT1 at the IFNgamma receptor complex, which is required for STAT1 DNA-binding activity. NKLAM-deficient macrophages show hyperphosphorylated JAK1 and STAT1 but reduced STAT1 DNA-binding ability and reduced IFNgamma-target gene expression. NKLAM is transiently localized to the IFNgamma receptor complex during stimulation. K63-specific ubiquitination assay, co-immunoprecipitation, NKLAM-KO macrophages, DNA-binding (GAS sequence) assay, gene expression analysis Cellular signalling Medium 27570112
2016 STAT1 directly binds a regulatory element (NRE1) in the first intron of the Nampt gene during IFNgamma stimulation, driving NAMPT expression. NAMPT, the rate-limiting enzyme in NAD salvage synthesis, supports STAT1-dependent M1 macrophage gene expression through its impact on glycolytic processes. Chromatin immunoprecipitation (ChIP), NRE1 disruption mouse model, NAMPT inhibition, scRNAseq Nature communications Medium 33976173
2016 STAT1 transcriptionally suppresses ULK1 (a kinase that controls autophagy initiation) by binding a regulatory sequence in the ULK1 5'-flanking region; mutation of this sequence increases ULK1 promoter activity and renders it unresponsive to mTOR inhibition. STAT1-deficient cells and mice show enhanced autophagic flux and increased ULK1 expression. Chromatin immunoprecipitation, promoter reporter assay with site mutation, STAT1-deficient cells and mice, autophagic flux measurements The Journal of biological chemistry High 28011640
2019 STAT1 (pSTAT1) directly binds the FOXM1 promoter to transcriptionally down-regulate FOXM1 expression, as demonstrated by dual-luciferase reporter and ChIP assays. IFNgamma-mediated STAT1 phosphorylation suppresses FOXM1 and sensitizes pancreatic cancer cells to gemcitabine. Chromatin immunoprecipitation, dual-luciferase reporter assay, IFNgamma treatment, in vitro and in vivo cell models Clinical science Medium 30782607
2020 In naive cells, unphosphorylated STAT2 forms a heterodimer with unphosphorylated STAT1 in an inactive anti-parallel conformation. A novel phosphorylation of STAT2 at Thr404 (mouse Thr403) by IKK-epsilon (activated by viral infection) disrupts this U-STAT1-U-STAT2 dimer, facilitating tyrosine phosphorylation of STAT1 and STAT2 and enhancing ISGF3 DNA-binding activity. Mice with T403A knockin are highly susceptible to viral infection. Electron microscopy structural analysis, site-directed mutagenesis (T404A), IKK-epsilon kinase assay, T403A knockin mice, ISGF3 DNA-binding assay Cell research High 32759968
2023 Nuclear RNA helicase DHX9 directly binds STAT1 upon IFN stimulation and recruits RNA Pol II to interferon-stimulated gene (ISG) promoter regions to facilitate STAT1-mediated ISG transcription. In vivo DHX9 knockout (myeloid- or hepatocyte-specific) combined with STAT1 knockout demonstrates that DHX9 acts downstream of type I IFN and requires STAT1 for antiviral gene regulation. Co-immunoprecipitation of DHX9-STAT1, chromatin immunoprecipitation (Pol II recruitment), conditional DHX9/STAT1 double-knockout mice, antiviral challenge Science advances Medium 36735791
2017 STAT1 acts downstream of PDGFRbeta signaling to mediate autoinflammation and tissue wasting. Genetic knockout of Stat1 in Pdgfrb gain-of-function mice rescues autoinflammation and converts the wasting phenotype to overgrowth. Deletion of IFN receptors (Ifnar1 or Ifngr1) does not rescue the Pdgfrb wasting phenotype, demonstrating that STAT1 mediates PDGFRbeta-driven autoinflammation independently of IFN receptor signaling. Genetic epistasis (Stat1-/- x Pdgfrb+/D849V double mutants), Ifnar1 and Ifngr1 knockout crosses, phenotypic analysis Genes & development High 28924035
2024 LPS-induced Toll-like receptor 4 endocytosis activates IκB kinase (IKK), which phosphorylates STAT1 at Thr748. This Thr748 phosphorylation promotes macrophage inflammatory responses while restricting IFN and anti-inflammatory responses. Phospho-deficient T748A knockin mice are resistant to LPS-induced lethality without disrupting canonical IFN-Tyr701 signaling, establishing Thr748 as an IFN-independent inflammatory phosphorylation switch. Genetically engineered T748A knockin mice, IKK kinase assay, LPS challenge model, macrophage depletion, phosphorylation site-specific analysis Proceedings of the National Academy of Sciences of the United States of America High 38621137
2019 STAT1 gain-of-function (GOF) pathogenic variants cause elevated total STAT1 protein levels (via increased STAT1 mRNA) rather than impaired dephosphorylation. The rate of STAT1 dephosphorylation after JAK inhibition is actually faster in GOF patient cells than healthy controls. The elevated peak pSTAT1 in GOF patients is driven by higher total STAT1 protein available for phosphorylation. Flow cytometry (total STAT1 protein), immunoblot, qRT-PCR (mRNA), cycloheximide chase (protein degradation), JAK inhibitor (ruxolitinib) dephosphorylation kinetics in patient PBMCs Frontiers in immunology Medium 31354696
2021 CCT6A interacts with STAT1 protein and protects it from ubiquitin-mediated proteasomal degradation, thereby stabilizing STAT1. Stabilized STAT1 then promotes transcription of hexokinase 2 (HK2), driving aerobic glycolysis in lung adenocarcinoma cells. Co-immunoprecipitation, mass spectrometry, chromatin immunoprecipitation, ubiquitination assay, CCT6A silencing Journal of translational medicine Medium 38750462
2022 ADAP (adhesion and degranulation-protein adaptor protein) interacts with STAT1 and competes with importin alpha5 for STAT1 binding, thereby restraining STAT1 nuclear entry. ADAP deficiency potentiates STAT1 nuclear translocation, leading to enhanced FcγRI/IV transcription and increased macrophage phagocytosis. Pharmacological inhibition of STAT1 or disruption of the STAT1-importin alpha5 interaction relieves thrombocytopenia in Adap-/- mice. Co-immunoprecipitation (ADAP-STAT1-importin α5 complex), ADAP-/- mice, STAT1 nuclear translocation assay, FcγR gene expression, pharmacological STAT1 inhibition Cellular & molecular immunology Medium 35637282
2023 STAT1 transcriptionally suppresses ULK1 (Ulk1) expression in microglia. Alpha-synuclein PFF activates STAT1 through Toll-like receptor 4-dependent signaling, causing STAT1-mediated suppression of Ulk1 transcription and impairment of microglial autophagy. Conditional microglial Stat1 knockout restores ULK1 expression and autophagy. Luciferase reporter assay (Ulk1 promoter), Stat1 knockdown and overexpression, conditional microglial Stat1-KO mice, TLR4 dependency analysis, autophagy flux measurements Journal of neuroinflammation Medium 39462396
2023 STAT1 is phosphorylated and activated by MST4 kinase in macrophages; MST4 silencing directly inhibits STAT1 phosphorylation, which is essential for M1 macrophage polarization. Macrophage-specific Mst4 knockout in an ITP mouse model reduces M1 macrophage numbers and attenuates thrombocytopenia. Co-immunoprecipitation, mass spectrometry, phosphoproteomics, RNA-seq, Mst4 conditional knockout mice, macrophage M1 polarization assays Cellular & molecular immunology Medium 37833401
2018 IRF1 promotes STAT1 phosphorylation at Tyr701 and subsequent GAS-element DNA binding through an indirect mechanism requiring IRF1 transactivation domain-dependent gene products (not direct IRF1-STAT1 interaction). IRF1-induced STAT1 activation is not blocked by IFN-beta or IFN-gamma antibodies, suggesting a novel cytokine mediates the effect. IRF1 deficiency reduces IFN-gamma-induced STAT1 phosphorylation persistence, establishing a positive feedback loop. Transient IRF1 overexpression in HEK293 cells, GAS-reporter assay, JAK1 phosphorylation analysis, IRF1-knockout cells (CRISPR), IRF1 complementation Immunology and cell biology Medium 29893425
2024 PRMT6 and STAT1 interact and synergistically regulate transcription of ACSL1. PRMT6 downregulation in diabetic nephropathy allows STAT1 to drive increased ACSL1 expression, promoting lipid peroxidation and ferroptosis in kidney cells. STAT1-specific inhibitor fludarabine delays DN progression in mouse models. Co-immunoprecipitation (PRMT6-STAT1), chromatin immunoprecipitation (STAT1 at ACSL1 promoter), PRMT6-/- mice, lipidomic analysis Cell death and differentiation Medium 39134684
2020 STAT1 functions as a transcriptional suppressor of HIF1A by binding to the HIF1A promoter. Ablation of ATG7 upregulates STAT1 expression (via a ZNF148-dependent autophagy-independent mechanism), increases STAT1 binding to the HIF1A promoter, and suppresses HIF1A expression, thereby inhibiting angiogenesis. Chromatin immunoprecipitation (STAT1 binding HIF1A promoter), endothelial-specific Atg7 KO mice, fludarabine STAT1 inhibition, tube formation assay Autophagy Medium 36300763
2021 Bcl6 directly binds the Stat1 promoter (demonstrated by ChIP) and transcriptionally represses Stat1 expression in osteoblasts. Loss of Bcl6 elevates Stat1 mRNA and protein, which attenuates nuclear translocation of Runx2, inhibiting osteoblast differentiation. Double knockout of Bcl6 and Stat1 rescues the bone phenotype of Bcl6-deficient mice. Chromatin immunoprecipitation (Bcl6 at Stat1 promoter), Bcl6-/- x Stat1-/- double-knockout mice, osteoblast differentiation assays Biochemical and biophysical research communications Medium 25597995
2020 S-glutathionylation of STAT1 (oxidative modification) induced by oxidative stress causes aberrant hyperactivation of STAT1 signaling in microglia, contributing to neuroinflammation under hypoxia. Both phosphorylation and S-glutathionylation of STAT1 are induced by hypoxia and drive M1 microglia activation. S-glutathionylation assay, STAT1 silencing, hypoxia model in BV2 cells, M1 phenotype markers Archives of biochemistry and biophysics Low 31121156
2017 STAT1 occupies a conserved binding element at IRF1 and STAT1 co-regulated ISG enhancers. IRF1 binds proximal or distant ISG sites more frequently than STAT1, and STAT1 almost always binds together with IRF1, while most IRF1 binding events are isolated. Dual STAT1+IRF1 binding at remote or proximal enhancers distinguishes IFNgamma-responsive from cell-type-resistant ISGs. ChIP-seq (STAT1 and IRF1 binding in multiple cell types), in vitro EMSA with SNP variants, in vivo ChIP validation BMC molecular biology Medium 28274199
2020 STAT1 directly binds the upstream region (-29 to -12 bp) of the S1PR1 promoter and stimulates S1PR1 transcription. STAT1 knockdown reduces S1PR1 mRNA and protein; STAT1 overexpression increases S1PR1 levels. IFN-gamma activation of STAT1 increases S1PR1 expression. EMSA, chromatin immunoprecipitation, promoter-deletion reporter assay, STAT1 knockdown and overexpression Gene Medium 32006593

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma. Science (New York, N.Y.) 744 7690989
1994 Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions. Cell 725 7510216
1992 Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. Proceedings of the National Academy of Sciences of the United States of America 602 1502203
1998 Inhibition of Stat1-mediated gene activation by PIAS1. Proceedings of the National Academy of Sciences of the United States of America 586 9724754
1992 The proteins of ISGF-3, the interferon alpha-induced transcriptional activator, define a gene family involved in signal transduction. Proceedings of the National Academy of Sciences of the United States of America 490 1502204
2014 JAK/STAT1 signaling promotes HMGB1 hyperacetylation and nuclear translocation. Proceedings of the National Academy of Sciences of the United States of America 301 24469805
2009 A phosphorylation-acetylation switch regulates STAT1 signaling. Genes & development 243 19171783
2016 PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation. Nature communications 238 27796300
2005 Structural bases of unphosphorylated STAT1 association and receptor binding. Molecular cell 238 15780933
2006 STAT1 as a key modulator of cell death. Cellular signalling 237 17085014
2015 The good and the bad faces of STAT1 in solid tumours. Cytokine 227 26631912
2012 STAT1 and STAT3 in tumorigenesis: A matter of balance. JAK-STAT 224 24058752
2006 Acetylation of Stat1 modulates NF-kappaB activity. Genes & development 196 16481475
2008 Ups and downs: the STAT1:STAT3 seesaw of Interferon and gp130 receptor signalling. Seminars in cell & developmental biology 192 18620071
2000 Distinct requirements for IFNs and STAT1 in NK cell function. Journal of immunology (Baltimore, Md. : 1950) 170 11034357
2020 Redox Regulation of STAT1 and STAT3 Signaling. International journal of molecular sciences 168 32987855
1994 Angiotensin II stimulates sis-inducing factor-like DNA binding activity. Evidence that the AT1A receptor activates transcription factor-Stat91 and/or a related protein. The Journal of biological chemistry 150 7527386
2013 NF-κB and STAT1 control CXCL1 and CXCL2 gene transcription. American journal of physiology. Endocrinology and metabolism 149 24280128
1994 Transcription factor ISGF-3 formation requires phosphorylated Stat91 protein, but Stat113 protein is phosphorylated independently of Stat91 protein. Proceedings of the National Academy of Sciences of the United States of America 138 8197134
2019 STAT1 drives M1 microglia activation and neuroinflammation under hypoxia. Archives of biochemistry and biophysics 132 31121156
2005 Opposing actions of STAT-1 and STAT-3. Growth factors (Chur, Switzerland) 128 16243709
2003 DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1. Genes & development 128 12923054
2017 STAT1 in cancer: friend or foe? Discovery medicine 127 28950072
2010 STAT1 and pathogens, not a friendly relationship. Biochimie 117 20159032
1994 Rapid changes in nuclear protein tyrosine phosphorylation after growth hormone treatment in vivo. Identification of phosphorylated mitogen-activated protein kinase and STAT91. The Journal of biological chemistry 117 7510676
2009 STAT1 pathway mediates amplification of metastatic potential and resistance to therapy. PloS one 107 19503789
2020 Regulation of the linear ubiquitination of STAT1 controls antiviral interferon signaling. Nature communications 101 32123171
2000 Divergent roles of STAT1 and STAT5 in malignancy as revealed by gene disruptions in mice. Oncogene 91 10851049
1998 STAT1 is inactivated by a caspase. The Journal of biological chemistry 90 9535846
2013 The tumor suppressor function of STAT1 in breast cancer. JAK-STAT 88 24058806
2009 Phosphorylation-acetylation switch in the regulation of STAT1 signaling. Molecular and cellular endocrinology 86 19879327
2013 STAT1 expression and activation is increased in lesional psoriatic skin. The British journal of dermatology 81 23013371
2006 Decreased STAT1 expression by promoter methylation in squamous cell carcinogenesis. Journal of the National Cancer Institute 74 16449678
2010 STAT1 interacts directly with cyclin D1/Cdk4 and mediates cell cycle arrest. Cell cycle (Georgetown, Tex.) 72 21084836
2001 STAT1 from the cell membrane to the DNA. The EMBO journal 69 11350940
2023 Ferroptosis triggered by STAT1- IRF1-ACSL4 pathway was involved in radiation-induced intestinal injury. Redox biology 68 37611494
2022 Unique aspects of IFN-γ/STAT1 signaling in neurons. Immunological reviews 61 35656941
2003 IFNalpha regulates NK cell cytotoxicity through STAT1 pathway. Cytokine 58 12967644
2019 STAT1 Gain-of-Function Mutations Cause High Total STAT1 Levels With Normal Dephosphorylation. Frontiers in immunology 57 31354696
2016 Tannic acid inhibits EGFR/STAT1/3 and enhances p38/STAT1 signalling axis in breast cancer cells. Journal of cellular and molecular medicine 55 27862996
2003 The ins and outs of STAT1 nuclear transport. Science's STKE : signal transduction knowledge environment 55 12915721
2013 Rotavirus NSP1 protein inhibits interferon-mediated STAT1 activation. Journal of virology 53 24131713
2008 IFN-gamma and STAT1 arrest monocyte migration and modulate RAC/CDC42 pathways. Journal of immunology (Baltimore, Md. : 1950) 53 18523269
2007 Transcription protein STAT1: biology and relation to cancer. Folia biologica 53 17328836
2021 Critical role of Syk-dependent STAT1 activation in innate antiviral immunity. Cell reports 48 33472080
2004 Protein kinase Cdelta regulates apoptosis via activation of STAT1. The Journal of biological chemistry 47 15322115
2021 A Stat1 bound enhancer promotes Nampt expression and function within tumor associated macrophages. Nature communications 46 33976173
2018 IRF1 supports DNA binding of STAT1 by promoting its phosphorylation. Immunology and cell biology 45 29893425
2020 A virus-induced conformational switch of STAT1-STAT2 dimers boosts antiviral defenses. Cell research 43 32759968
2019 STAT1-mediated inhibition of FOXM1 enhances gemcitabine sensitivity in pancreatic cancer. Clinical science (London, England : 1979) 41 30782607
2023 MST4 kinase regulates immune thrombocytopenia by phosphorylating STAT1-mediated M1 polarization of macrophages. Cellular & molecular immunology 40 37833401
2006 Stat1 and SUMO modification. Blood 40 16857984
2024 The PRMT6/STAT1/ACSL1 axis promotes ferroptosis in diabetic nephropathy. Cell death and differentiation 39 39134684
2017 STAT1 modulates tissue wasting or overgrowth downstream from PDGFRβ. Genes & development 39 28924035
2013 STAT1 negatively regulates hepatocellular carcinoma cell proliferation. Oncology reports 39 23588992
2017 Properties of STAT1 and IRF1 enhancers and the influence of SNPs. BMC molecular biology 38 28274199
2005 IFNgammaR2 trafficking tunes IFNgamma-STAT1 signaling in T lymphocytes. Trends in immunology 38 16380292
2016 Regulation of ULK1 Expression and Autophagy by STAT1. The Journal of biological chemistry 37 28011640
2012 Inhibition of STAT1 sensitizes renal cell carcinoma cells to radiotherapy and chemotherapy. Cancer biology & therapy 37 22262126
2021 Mettl3 promotes oxLDL-mediated inflammation through activating STAT1 signaling. Journal of clinical laboratory analysis 36 34825733
2020 Upregulated PKM2 in Macrophages Exacerbates Experimental Arthritis via STAT1 Signaling. Journal of immunology (Baltimore, Md. : 1950) 36 32503893
2005 Stat1-mediated cytoplasmic attenuation in osteoimmunology. Journal of cellular biochemistry 35 15546140
2020 STAT1 Dissociates Adipose Tissue Inflammation From Insulin Sensitivity in Obesity. Diabetes 33 32994273
2003 The PKR kinase promoter binds both Sp1 and Sp3, but only Sp3 functions as part of the interferon-inducible complex with ISGF-3 proteins. Virology 33 12954221
1998 Cooperative binding of Stat1-2 heterodimers and ISGF3 to tandem DNA elements. Biochimie 33 9865492
2020 RNF220 mediates K63-linked polyubiquitination of STAT1 and promotes host defense. Cell death and differentiation 32 32814877
2014 Increased STAT1 signaling in endocrine-resistant breast cancer. PloS one 32 24728078
2019 Activation of the STAT1 Pathway Accelerates Periodontitis in Nos3 Mice. Journal of dental research 30 31329047
2017 Unphosphorylated STAT1 represses apoptosis in macrophages during Mycobacteriumtuberculosis infection. Journal of cell science 30 28348106
2024 CCT6A facilitates lung adenocarcinoma progression and glycolysis via STAT1/HK2 axis. Journal of translational medicine 29 38750462
2019 PHLPP1 counter-regulates STAT1-mediated inflammatory signaling. eLife 29 31408005
2023 Nucleic DHX9 cooperates with STAT1 to transcribe interferon-stimulated genes. Science advances 28 36735791
2022 Ablation of endothelial Atg7 inhibits ischemia-induced angiogenesis by upregulating Stat1 that suppresses Hif1a expression. Autophagy 28 36300763
2021 CITED2 inhibits STAT1-IRF1 signaling and atherogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 34365659
2022 Transcriptional expression of CXCL10 and STAT1 in lupus nephritis and the intervention effect of triptolide. Clinical rheumatology 25 36374433
2017 Steering of carcinoma progression by the YIN/YANG interaction of STAT1/STAT3. Bioscience trends 25 28154246
2017 Involvement of STAT1 in proliferation and invasiveness of trophoblastic cells. Reproductive biology 25 28552376
2015 Bcl6 promotes osteoblastogenesis through Stat1 inhibition. Biochemical and biophysical research communications 25 25597995
2021 CPVL promotes glioma progression via STAT1 pathway inhibition through interactions with the BTK/p300 axis. JCI insight 23 34784299
2016 E3 ubiquitin ligase NKLAM ubiquitinates STAT1 and positively regulates STAT1-mediated transcriptional activity. Cellular signalling 23 27570112
2013 Computational models of the JAK1/2-STAT1 signaling. JAK-STAT 23 24069559
1995 Induction of expression of interferon-stimulated gene factor-3 (ISGF-3) proteins by interferons. Experimental cell research 23 7529187
2022 ADAP restraint of STAT1 signaling regulates macrophage phagocytosis in immune thrombocytopenia. Cellular & molecular immunology 22 35637282
2021 circSVIL regulates bovine myoblast development by inhibiting STAT1 phosphorylation. Science China. Life sciences 22 34024027
2020 Lyssavirus P-protein selectively targets STAT3-STAT1 heterodimers to modulate cytokine signalling. PLoS pathogens 22 32903273
2016 Analysis of STAT1 expression and biological activity reveals interferon-tau-dependent STAT1-regulated SOCS genes in the bovine endometrium. Reproduction, fertility, and development 22 25116692
2018 RNF168 facilitates proliferation and invasion of esophageal carcinoma, possibly via stabilizing STAT1. Journal of cellular and molecular medicine 21 30506884
1994 Mutant cell lines unresponsive to alpha/beta and gamma interferon are defective in tyrosine phosphorylation of ISGF-3 alpha components. Molecular and cellular biology 20 8114747
2024 Threonine phosphorylation of STAT1 restricts interferon signaling and promotes innate inflammatory responses. Proceedings of the National Academy of Sciences of the United States of America 19 38621137
2017 ERK expression and its correlation with STAT1 in esophageal squamous cell carcinoma. Oncotarget 19 28431406
2024 PVT1 promotes proliferation and macrophage immunosuppressive polarization through STAT1 and CX3CL1 regulation in glioblastoma multiforme. CNS neuroscience & therapeutics 18 38287522
2023 Human cytomegalovirus UL138 interaction with USP1 activates STAT1 in infection. PLoS pathogens 18 37289831
2023 Prolonged STAT1 activation in neurons drives a pathological transcriptional response. Journal of neuroimmunology 18 37556887
2020 Fibroblast-specific Stat1 deletion enhances the myofibroblast phenotype during tissue repair. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 18 32175700
2019 Early Pregnancy Induces Expression of STAT1, OAS1 and CXCL10 in Ovine Spleen. Animals : an open access journal from MDPI 17 31671580
2018 Dichotomal functions of phosphorylated and unphosphorylated STAT1 in hepatocellular carcinoma. Journal of molecular medicine (Berlin, Germany) 17 30456450
2020 STAT1 transcriptionally regulates the expression of S1PR1 by binding its promoter region. Gene 16 32006593
2020 STAT1 expression and HPV16 viral load predict cervical lesion progression. Oncology letters 16 32774501
2007 STAT1 gene variations, IgE regulation and atopy. Allergy 16 17983380
2024 α-Synuclein disrupts microglial autophagy through STAT1-dependent suppression of Ulk1 transcription. Journal of neuroinflammation 15 39462396

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