STAT2

Summary

Gene Symbol: STAT2
Description: signal transducer and activator of transcription 2
Alias: IMD44, ISGF-3, P113, STAT113, signal transducer and activator of transcription 2, interferon alpha induced transcriptional activator, signal transducer and activator of transcription 2, 113kDa
Species: human
Products:     STAT2

Top Publications

  1. Fu X, Schindler C, Improta T, Aebersold R, Darnell J. The proteins of ISGF-3, the interferon alpha-induced transcriptional activator, define a gene family involved in signal transduction. Proc Natl Acad Sci U S A. 1992;89:7840-3 pubmed
    ..We suggest that proteins encoded by this gene family serve the function of interpreting the fact that a cell surface receptor has bound its ligand so that specific signal transduction to the nucleus can occur. ..
  2. Bhattacharya S, Eckner R, Grossman S, Oldread E, Arany Z, D ANDREA A, et al. Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha. Nature. 1996;383:344-7 pubmed
    ..Adenovirus E1A blocks the IFN-alpha response, allowing unhindered viral replication. ISGF3 consists of Stat1, Stat2 and p48...
  3. Bluyssen H, Levy D. Stat2 is a transcriptional activator that requires sequence-specific contacts provided by stat1 and p48 for stable interaction with DNA. J Biol Chem. 1997;272:4600-5 pubmed
    ..Responses to type I IFN (alpha and beta) also require Stat2 and the IFN regulatory factor family protein p48, which form a heterotrimeric transcription complex with Stat1 ..
  4. Martinez Moczygemba M, Gutch M, French D, Reich N. Distinct STAT structure promotes interaction of STAT2 with the p48 subunit of the interferon-alpha-stimulated transcription factor ISGF3. J Biol Chem. 1997;272:20070-6 pubmed
    ..The functions of the individual STATs are dependent on distinct protein-protein interactions. STAT1 and STAT2 are activated by tyrosine phosphorylation in response to type I interferons-alpha/beta (IFN-alpha/beta) and ..
  5. Parisien J, Lau J, Rodriguez J, Ulane C, Horvath C. Selective STAT protein degradation induced by paramyxoviruses requires both STAT1 and STAT2 but is independent of alpha/beta interferon signal transduction. J Virol. 2002;76:4190-8 pubmed
    ..genus of the Paramyxovirus family of RNA viruses have acquired the ability to specifically target either STAT1 or STAT2 for proteolytic degradation as a countermeasure for evading IFN responses...
  6. Fagerlund R, Melen K, Kinnunen L, Julkunen I. Arginine/lysine-rich nuclear localization signals mediate interactions between dimeric STATs and importin alpha 5. J Biol Chem. 2002;277:30072-8 pubmed
    ..Here we show that baculovirus-produced and -activated STAT1 homodimers and STAT1-STAT2 heterodimers directly interacted with importin alpha 5 (NPI-1)...
  7. Nusinzon I, Horvath C. Interferon-stimulated transcription and innate antiviral immunity require deacetylase activity and histone deacetylase 1. Proc Natl Acad Sci U S A. 2003;100:14742-7 pubmed
    ..The HDAC1 protein associates with both signal transducer and activator of transcription (STAT) 1 and STAT2, and IFN-alpha stimulation induces deacetylation of histone H4...
  8. Banninger G, Reich N. STAT2 nuclear trafficking. J Biol Chem. 2004;279:39199-206 pubmed
    b>STAT2 is a transcription factor critical to the signal transduction pathway of type I interferons (e.g. IFNalpha). STAT2 resides primarily in the cytoplasm and is tyrosine-phosphorylated after IFNalpha binds to cell surface receptors...
  9. Lin W, Choe W, Hiasa Y, Kamegaya Y, Blackard J, Schmidt E, et al. Hepatitis C virus expression suppresses interferon signaling by degrading STAT1. Gastroenterology. 2005;128:1034-41 pubmed
    ..HCV core, but not HCV E1, E2, NS3, NS4, or NS5, bound to STAT1. STAT2 expression was not affected by HCV...

More Information

Publications114 found, 100 shown here

  1. Tang X, Gao J, Guan Y, McLane K, Yuan Z, Ramratnam B, et al. Acetylation-dependent signal transduction for type I interferon receptor. Cell. 2007;131:93-105 pubmed
    ..means of its IRF homology2 (IH2) domain, leading to formation of the ISGF3 complex that includes IRF9, STAT1, and STAT2. All three components are acetylated by CBP...
  2. Mazzon M, Jones M, Davidson A, Chain B, Jacobs M. Dengue virus NS5 inhibits interferon-alpha signaling by blocking signal transducer and activator of transcription 2 phosphorylation. J Infect Dis. 2009;200:1261-70 pubmed publisher
    ..NS5 binds signal transducer and activator of transcription 2 (STAT2) and inhibits its phosphorylation...
  3. Huh Y, Kim Y, Kim E, Park J, Song M, Zhu H, et al. Binding STAT2 by the acidic domain of human cytomegalovirus IE1 promotes viral growth and is negatively regulated by SUMO. J Virol. 2008;82:10444-54 pubmed publisher
    ..We found that the acidic domain of IE1 is required for binding to STAT2. A mutant HCMV encoding IE1(Delta421-475) with the acidic domain deleted was generated...
  4. Ashour J, Laurent Rolle M, Shi P, Garcia Sastre A. NS5 of dengue virus mediates STAT2 binding and degradation. J Virol. 2009;83:5408-18 pubmed publisher
    ..In addition, DENV infection results in reduced levels of expression of STAT2, which is required for IFN signaling (M. Jones, A. Davidson, L. Hibbert, P. Gruenwald, J. Schlaak, S. Ball, G. R...
  5. Romero Weaver A, Wang H, Steen H, Scarzello A, Hall V, Sheikh F, et al. Resistance to IFN-alpha-induced apoptosis is linked to a loss of STAT2. Mol Cancer Res. 2010;8:80-92 pubmed publisher
    ..resistance to type I IFN-induced apoptosis due to a loss of signal transducers and activators of transcription 2 (STAT2) expression...
  6. Ashour J, Morrison J, Laurent Rolle M, Belicha Villanueva A, Plumlee C, Bernal Rubio D, et al. Mouse STAT2 restricts early dengue virus replication. Cell Host Microbe. 2010;8:410-21 pubmed publisher
    Dengue virus encodes several interferon antagonists. Among these the NS5 protein binds STAT2, a necessary component of the type I interferon signaling pathway, and targets it for degradation...
  7. Ojha A, Bhasym A, Mukherjee S, Annarapu G, Bhakuni T, Akbar I, et al. Platelet factor 4 promotes rapid replication and propagation of Dengue and Japanese encephalitis viruses. EBioMedicine. 2019;39:332-347 pubmed publisher
    ..cytokine analysis and immunoblot assay showed significant inhibition of IFN-α production in monocytes via p38MAPK-STAT2-IRF9 axis. Blocking PF4 through antibodies or its receptor CXCR3 through inhibitor i.e...
  8. Lorenzini T, Dotta L, Giacomelli M, Vairo D, Badolato R. STAT mutations as program switchers: turning primary immunodeficiencies into autoimmune diseases. J Leukoc Biol. 2017;101:29-38 pubmed publisher
    ..b>STAT2 deficiency has been described in 5 family members and is characterized by selective susceptibility to viral ..
  9. Hermann B, Wuertz S, Vanselow K, Schulz C, Stiller K. Divergent gene expression in the gills of juvenile turbot (Psetta maxima) exposed to chronic severe hypercapnia indicates dose-dependent increase in intracellular oxidative stress and hypoxia. Aquat Toxicol. 2019;206:72-80 pubmed publisher
    ..anti-oxidant activity and regulation of transcription, while reduced mRNA concentrations of COX, EF1α and STAT2 at high CO2 denoted suppressed protein synthesis and reduced metabolic capacity...
  10. Li S, Yang L, Wang P, He Y, Huang J, Liu H, et al. Dietary apigenin potentiates the inhibitory effect of interferon-α on cancer cell viability through inhibition of 26S proteasome-mediated interferon receptor degradation. Food Nutr Res. 2016;60:31288 pubmed publisher
    ..Apigenin enhanced the phosphorylation of signal transducer and activator of transcription proteins (STAT1 and STAT2) and promoted the endogenous IFN-α-regulated gene expression...
  11. Chen Y, Xu Q, Li Y, Liu R, Huang Z, Wang B, et al. Gene expression profile after activation of RIG-I in 5'ppp-dsRNA challenged DF1. Dev Comp Immunol. 2016;65:191-200 pubmed publisher
    ..of key responsive genes in RIG-I-mediated signaling pathways, such as ISG12-2, Mx1, IFIT5, TRIM25, USP18, STAT1, STAT2, IRF1, IRF7 and IRF8, were tested for differential expression by real-time RT-PCR...
  12. Araldi E, Fernández Fuertes M, Canfrán Duque A, Tang W, Cline G, Madrigal Matute J, et al. Lanosterol Modulates TLR4-Mediated Innate Immune Responses in Macrophages. Cell Rep. 2017;19:2743-2755 pubmed publisher
    ..in mouse macrophages in vitro, decreases IFNβ-mediated signal transducer and activator of transcription (STAT)1-STAT2 activation and IFNβ-stimulated gene expression...
  13. Du J, Chen X, Wang C, Sun H. Pathway analysis of global gene expression change in dendritic cells induced by the polysaccharide from the roots of Actinidia eriantha. J Ethnopharmacol. 2018;214:141-152 pubmed publisher
    ..IL-10, IL-12p40, IFN-? and IFN-?), chemokines (MIP-1?, MIP-1?, CCL5, MDC and MCP-1), transcription factors (STAT1, STAT2, STAT5b, IRF1 and IRF7) and pattern recognition receptors (TLR3, DDX58, DHX58 and IFIH1) in the BMDCs...
  14. Ko E, Chorich L, Sullivan M, Cameron R, Layman L. JAK/STAT signaling pathway gene expression is reduced following Nelf knockdown in GnRH neurons. Mol Cell Endocrinol. 2018;470:151-159 pubmed publisher
    ..of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, including Stat1, Stat2, Stat5a, Jak2, Irf7 and Irf9, were significantly down regulated as assessed by RT-qPCR...
  15. van der Kroef M, Castellucci M, Mokry M, Cossu M, Garonzi M, Bossini Castillo L, et al. Histone modifications underlie monocyte dysregulation in patients with systemic sclerosis, underlining the treatment potential of epigenetic targeting. Ann Rheum Dis. 2019;78:529-538 pubmed publisher
    ..IFNα induced the binding of STAT1 and STAT2 at the promoter of two of these genes, while blocking acetylation readers using the bromodomain BET family ..
  16. Walter K, Goodman M, Singhal H, Hall J, Li T, Holloran S, et al. Interferon-Stimulated Genes Are Transcriptionally Repressed by PR in Breast Cancer. Mol Cancer Res. 2017;15:1331-1340 pubmed publisher
    ..to PR activation, key regulatory transcription factors that are required for IFN-activated ISG transcription, STAT2 and IRF9, exhibit impaired recruitment to ISG promoter regions, correlating with PR/ligand-dependent ISG ..
  17. Xiang Y, Liu W, Jia P, Li Y, Jin Y, Chen L, et al. Molecular characterization and expression analysis of interferon-gamma in black seabream Acanthopagrus schlegelii. Fish Shellfish Immunol. 2017;70:140-148 pubmed publisher
    ..rapidly and transiently stimulated the expression of JAK-STAT signaling pathway related genes including STAT1, STAT2 and IRF9, as well as the downstream antiviral genes MX1 and ISG15...
  18. George C, Ramaswami G, Li J, Samuel C. Editing of Cellular Self-RNAs by Adenosine Deaminase ADAR1 Suppresses Innate Immune Stress Responses. J Biol Chem. 2016;291:6158-68 pubmed publisher
    ..editing in both WT and Adar2(-/-) cells but not in either Adar1(-/-) or Adar1(-/-) (p150) cells or Stat1(-/-) or Stat2(-/-) cells. Hyper-edited sites found in predicted duplex structures showed strand bias of editing for some RNAs...
  19. Fantetti K, Gray E, Ganesan P, Kulkarni A, O Donnell L. Interferon gamma protects neonatal neural stem/progenitor cells during measles virus infection of the brain. J Neuroinflammation. 2016;13:107 pubmed publisher
    ..Phosphorylation of STAT1 and STAT2 occurred independently of IFNγ in the hippocampus, albeit with distinct regulation of activation...
  20. Malbon A, Meli M, Barker E, Davidson A, Tasker S, Kipar A. Inflammatory Mediators in the Mesenteric Lymph Nodes, Site of a Possible Intermediate Phase in the Immune Response to Feline Coronavirus and the Pathogenesis of Feline Infectious Peritonitis?. J Comp Pathol. 2019;166:69-86 pubmed publisher
    ..cats without FIP, there were few differences between virus-positive and virus-negative MLNs; however, TLR9 and STAT2 expression were higher with infection, suggesting a direct viral effect...
  21. Shiozaki A, Ariyoshi Y, Iitaka D, Kosuga T, Shimizu H, Kudou M, et al. Functional analysis and clinical significance of sodium iodide symporter expression in gastric cancer. Gastric Cancer. 2019;22:473-485 pubmed publisher
    ..results of the microarray analysis revealed that various interferon (IFN) signaling-related genes, such as STAT1, STAT2, IRF1, and IFIT1, were up-regulated in NIS-depleted MKN45 cells...
  22. Bazer F, Thatcher W. Chronicling the discovery of interferon tau. Reproduction. 2017;154:F11-F20 pubmed publisher
    ..But, IFNT signaling through a STAT1/STAT2-independent pathway stimulates expression of genes, such as those for transport of glucose and amino acids, which ..
  23. Kazezian Z, Li Z, Alini M, Grad S, Pandit A. Injectable hyaluronic acid down-regulates interferon signaling molecules, IGFBP3 and IFIT3 in the bovine intervertebral disc. Acta Biomater. 2017;52:118-129 pubmed publisher
    ..acts as an anti-inflammatory molecule by down-regulating IFNAR1 and IFNAR2, the signaling molecules STAT1, STAT2, JAK1 and the downstream apoptotic targets IGFBP3 and IFIT3...
  24. Vasou A, Paulus C, Narloch J, Gage Z, Rameix Welti M, Eléouët J, et al. Modular cell-based platform for high throughput identification of compounds that inhibit a viral interferon antagonist of choice. Antiviral Res. 2018;150:79-92 pubmed publisher
    ..identified (i) four hit compounds that specifically inhibit RSV NS2's ability to block IFN signaling by mediating STAT2 degradation and exhibit modest antiviral activity and (ii) two hit compounds that interfere with IE1 transcription ..
  25. Bagdassarian E, Doceul V, Pellerin M, Demange A, Meyer L, Jouvenet N, et al. The Amino-Terminal Region of Hepatitis E Virus ORF1 Containing a Methyltransferase (Met) and a Papain-Like Cysteine Protease (PCP) Domain Counteracts Type I Interferon Response. Viruses. 2018;10: pubmed publisher
    ..In contrast, MetYPCP had no effect on STAT2 phosphorylation and a limited impact on the activation of the JAK/STAT pathway after IFN-II stimulation...
  26. Nakamura K, Kusama K, Bai R, Sakurai T, Isuzugawa K, Godkin J, et al. Induction of IFNT-Stimulated Genes by Conceptus-Derived Exosomes during the Attachment Period. PLoS ONE. 2016;11:e0158278 pubmed publisher
    ..originated from the conceptus, contained interferon tau (IFNT) as well as CAPG and AKR1B1, and up-regulated STAT1, STAT2, MX1, MX2, BST2, and ISG15 transcripts in EECs...
  27. Guan G, Shen Y, Yu Q, Liu H, Zhang B, Guo Y, et al. Down-regulation of IFIT3 protects liver from ischemia-reperfusion injury. Int Immunopharmacol. 2018;60:170-178 pubmed publisher
    ..Furthermore, knockdown of IFIT3 inhibited phosphorylation of STAT1 and STAT2, and decreased expressions of IFN-stimulated genes induced by ischemia and reperfusion in vivo and in vitro...
  28. Shrivastava S, Meissner E, Funk E, Poonia S, Shokeen V, Thakur A, et al. Elevated hepatic lipid and interferon stimulated gene expression in HCV GT3 patients relative to non-alcoholic steatohepatitis. Hepatol Int. 2016;10:937-946 pubmed
    ..IFNAR1, IL10RB negative regulators of interferon signaling SOCS3, USP18, JAK/STAT and IRF family members STAT1, STAT2, and IRF, and TGFB family members TGFB1, TGFBR1, and TGFBR2 and other ISGs like OAS2, IF127, IF144 and ISG15...
  29. Zare F, Dehghan Manshadi M, Mirshafiey A. The signal transducer and activator of transcription factors lodge in immunopathogenesis of rheumatoid arthritis. Reumatismo. 2015;67:127-37 pubmed publisher
    ..All STAT family members (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6) have been associated with autoimmune diseases, as highlighted in several ..
  30. Viedma Rodríguez R, Ruiz Esparza Garrido R, Baiza Gutman L, Velázquez Flores M, García Carrancá A, Salamanca Gómez F, et al. Involvement of multiple cellular pathways in regulating resistance to tamoxifen in BIK-suppressed MCF-7 cells. Tumour Biol. 2015;36:6991-7005 pubmed publisher
    ..Transcriptional and translational analysis of key molecules such as STAT2, AKT 3, and 14-3-3z revealed similar changes at the messenger RNA (mRNA) as well as at the protein level...
  31. Imgenberg Kreuz J, Sandling J, Björk A, Nordlund J, Kvarnström M, Eloranta M, et al. Transcription profiling of peripheral B cells in antibody-positive primary Sjögren's syndrome reveals upregulated expression of CX3CR1 and a type I and type II interferon signature. Scand J Immunol. 2018;87:e12662 pubmed publisher
    ..TNFSF4/Ox40L, TNFSF10/TRAIL, TNFSF13B/BAFF, TNFRSF17/BCMA as well as S100A8 and -A9/calprotectin, TLR7, STAT1 and STAT2. Among genes with downregulated expression in pSS B cells were SOCS1 and SOCS3, CD70 and TNFAIP3/A20...
  32. Tovey M, Lallemand C. Safety, Tolerability, and Immunogenicity of Interferons. Pharmaceuticals (Basel). 2010;3:1162-1186 pubmed
    ..and activation of the latent cytoplasmic signal transducers and activators of transcription (STAT1) and STAT2, formation of a transcription complex together with IRF9, and activation of a specific set of genes that encode ..
  33. Abdul Sater A, Majoros A, Plumlee C, Perry S, Gu A, Lee C, et al. Different STAT Transcription Complexes Drive Early and Delayed Responses to Type I IFNs. J Immunol. 2015;195:210-216 pubmed publisher
    IFNs, which transduce pivotal signals through Stat1 and Stat2, effectively suppress the replication of Legionella pneumophila in primary murine macrophages. Although the ability of IFN-γ to impede L...
  34. Wu Z, Wang L, Xu X, Lin G, Mao H, Ran X, et al. Interaction of IRF9 and STAT2 synergistically up-regulates IFN and PKR transcription in Ctenopharyngodon idella. Mol Immunol. 2017;85:273-282 pubmed publisher
    IRF9 is a key factor in the JAK-STAT pathway. Under the stimulation of type I IFN, IRF9 interacts with STAT1 and STAT2 to form the IFN-I-stimulated gene factor 3 (ISGF3) which activates the transcription of ISG...
  35. Shou P, Chen Q, Jiang J, Xu C, Zhang J, Zheng C, et al. Type I interferons exert anti-tumor effect via reversing immunosuppression mediated by mesenchymal stromal cells. Oncogene. 2016;35:5953-5962 pubmed publisher
    ..IFNα promoted the switch from signal transducer and activator of transcription 1 (Stat1) homodimers to Stat1-Stat2 heterodimers...
  36. Hurtado Guerrero I, Pinto Medel M, Urbaneja P, Rodriguez Bada J, Leon A, Guerrero M, et al. Activation of the JAK-STAT Signaling Pathway after In Vitro Stimulation with IFNß in Multiple Sclerosis Patients According to the Therapeutic Response to IFNß. PLoS ONE. 2017;12:e0170031 pubmed publisher
    ..Therefore, cell surface levels of IFNAR subunits (IFNAR1 and IFNAR2) and the activated forms of STAT1 and STAT2 were assessed in peripheral blood mononuclear cells from MS patients by flow cytometry...
  37. Krishnan K, Singh B, Krolewski J. Identification of amino acid residues critical for the Src-homology 2 domain-dependent docking of Stat2 to the interferon alpha receptor. J Biol Chem. 1998;273:19495-501 pubmed
    ..The region surrounding phosphorylated tyrosine 466 subsequently acts as a docking site for the SH2 domain of Stat2, facilitating phosphorylation of the latter and, thus, the transduction of the IFNalpha signal...
  38. Rodriguez J, Wang L, Horvath C. Hendra virus V protein inhibits interferon signaling by preventing STAT1 and STAT2 nuclear accumulation. J Virol. 2003;77:11842-5 pubmed
    ..been shown to inhibit interferon (IFN) signal transduction through cytoplasmic sequestration of cellular STAT1 and STAT2 in high-molecular-weight complexes...
  39. Claudinon J, Gonnord P, Beslard E, Marchetti M, Mitchell K, Boularan C, et al. Palmitoylation of interferon-alpha (IFN-alpha) receptor subunit IFNAR1 is required for the activation of Stat1 and Stat2 by IFN-alpha. J Biol Chem. 2009;284:24328-40 pubmed publisher
    ..However, the lack of IFNAR1 palmitoylation affects selectively the activation of Stat2, which results in a lack of efficient Stat1 activation and nuclear translocation and IFN-alpha-activated gene ..
  40. Morrison J, Laurent Rolle M, Maestre A, Rajsbaum R, Pisanelli G, Simon V, et al. Dengue virus co-opts UBR4 to degrade STAT2 and antagonize type I interferon signaling. PLoS Pathog. 2013;9:e1003265 pubmed publisher
    ..DENV NS5 protein inhibits IFN-I signaling by mediating proteasome-dependent STAT2 degradation...
  41. Zhu M, Lu J, Dong X, Zheng N, Li T, Chen Z, et al. Interferon-stimulated gene factor 3 complex is required for the induction of sterile α motif and HD domain-containing protein 1 expression by interferon-α in SMMC-7721 cells. Mol Med Rep. 2015;12:7176-80 pubmed publisher
    ..Knockdown of STAT1 inhibited the induction of SAMHD1 expression by IFN‑α in SMMC‑7721 cells. STAT2 silencing also suppressed the induction of SAMHD1 expression by IFN‑α in SMMC‑7721 cells...
  42. Lindström I, Dogan J. Native Hydrophobic Binding Interactions at the Transition State for Association between the TAZ1 Domain of CBP and the Disordered TAD-STAT2 Are Not a Requirement. Biochemistry. 2017;56:4145-4153 pubmed publisher
    ..binding between the TAZ1 domain of CREB binding protein and the intrinsically disordered transactivation domain of STAT2 (TAD-STAT2) by site-directed mutagenesis and kinetic experiments (?-value analysis) and found that the native ..
  43. Yan R, Qureshi S, Zhong Z, Wen Z, Darnell J. The genomic structure of the STAT genes: multiple exons in coincident sites in Stat1 and Stat2. Nucleic Acids Res. 1995;23:459-63 pubmed
    The genomic structure of Stat2 has been determined and compared with a large portion of the Stat1 gene. There are 24 exons in the Stat2 gene and a matching number in very similar positions in the Stat1 gene...
  44. Yi T, Lee D, Jeon M, Kwon S, Song S. Gene expression profile reveals that STAT2 is involved in the immunosuppressive function of human bone marrow-derived mesenchymal stem cells. Gene. 2012;497:131-9 pubmed
    ..Among these, the ICOSLG and STAT2 genes were drastically upregulated 173-fold and 154-fold, respectively...
  45. Yuan Y, Fan J, Yao F, Wang K, Yu Y, Carlson J, et al. Association Study of Single-Nucleotide Polymorphisms of STAT2/STAT3/IFN-γ Genes in Cervical Cancer in Southern Chinese Han Women. Asian Pac J Cancer Prev. 2015;16:3117-20 pubmed
    ..Our objective was to evaluate the association of SNPs in STAT2, STAT3, and IFN-γ with cervical cancer susceptibility in Chinese Han women in Hunan province...
  46. Duncan C, Mohamad S, Young D, Skelton A, Leahy T, Munday D, et al. Human IFNAR2 deficiency: Lessons for antiviral immunity. Sci Transl Med. 2015;7:307ra154 pubmed publisher
    ..The phenotype of IFNAR2 deficiency, together with similar findings in STAT2-deficient patients, supports an essential but narrow role for IFN-α/β in human antiviral immunity.
  47. Price A, Tedesco D, Prasad M, Workowski K, Walker C, Suthar M, et al. Prolonged activation of innate antiviral gene signature after childbirth is determined by IFNL3 genotype. Proc Natl Acad Sci U S A. 2016;113:10678-83 pubmed publisher
    ..genes (ISGs) encoding proteins such as IFIT1, IFIT2, and IFIT3, as well as signaling proteins such as STAT1, STAT2, and MAVS, were enriched postpartum...
  48. Wang Y, Nan J, Willard B, Wang X, Yang J, Stark G. Negative regulation of type I IFN signaling by phosphorylation of STAT2 on T387. EMBO J. 2017;36:202-212 pubmed publisher
    ..We have discovered a novel phosphorylation of STAT2 on T387 that negatively regulates this response...
  49. Yan H, Krishnan K, Greenlund A, Gupta S, Lim J, Schreiber R, et al. Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 protein. EMBO J. 1996;15:1064-74 pubmed
    ..A phosphopeptide corresponding to the major phosphorylation site (Tyr466) binds STAT2, but not STAT1, in an SH-2-dependent manner...
  50. Zhang J, Yamada O, Kawagishi K, Araki H, Yamaoka S, Hattori T, et al. Human T-cell leukemia virus type 1 Tax modulates interferon-alpha signal transduction through competitive usage of the coactivator CBP/p300. Virology. 2008;379:306-13 pubmed publisher
    ..Gene activation induced by STAT2 transcription domain was also inhibited by expression of Tax...
  51. Hernandez J, Elahi A, Clark W, Humphries L, Wang J, Achille A, et al. The Tumor Suppressive Effects of HPP1 Are Mediated Through JAK-STAT-Interferon Signaling Pathways. DNA Cell Biol. 2015;34:541-9 pubmed publisher
    ..We previously demonstrated the importance of STAT1 activation for HPP1 function; however the contribution of STAT2 remains unclear...
  52. Hsu Y, Huang C, Kung Y, Lin H, Chang C, Lee K, et al. The anti-proliferative effects of type I IFN involve STAT6-mediated regulation of SP1 and BCL6. Cancer Lett. 2016;375:303-312 pubmed publisher
    ..IFN treatment did not increase Sp1 and BCL6 expression in a STAT2-deficient RST2 cell line, and this effect was mitigated by plasmid overexpression of STAT2, indicating that STAT2 ..
  53. Gowen B, Westover J, Miao J, Van Wettere A, Rigas J, Hickerson B, et al. Modeling Severe Fever with Thrombocytopenia Syndrome Virus Infection in Golden Syrian Hamsters: Importance of STAT2 in Preventing Disease and Effective Treatment with Favipiravir. J Virol. 2017;91: pubmed publisher
    ..Here, we demonstrate that hamsters devoid of functional STAT2 are highly susceptible to as few as 10 PFU of SFTSV, with animals generally succumbing within 5 to 6 days after ..
  54. Cebulla C, Miller D, Sedmak D. Viral inhibition of interferon signal transduction. Intervirology. 1999;42:325-30 pubmed
    ..Herein, we review the ability and novel mechanisms of several diverse viruses to inhibit IFN-induced JAK/STAT signal transduction. ..
  55. Lau J, Nusinzon I, Burakov D, Freedman L, Horvath C. Role of metazoan mediator proteins in interferon-responsive transcription. Mol Cell Biol. 2003;23:620-8 pubmed
    ..signal transduction and transcription activation complex, ISGF3, is assembled from three proteins, STAT1, STAT2, and IRF9...
  56. Fleetwood A, Dinh H, Cook A, Hertzog P, Hamilton J. GM-CSF- and M-CSF-dependent macrophage phenotypes display differential dependence on type I interferon signaling. J Leukoc Biol. 2009;86:411-21 pubmed publisher
    ..relative to GM-BMM, of a number of genes identified as being dependent on type I IFN signaling, including Stat1, Stat2, Irf7, Ccl5, Ccl12, and Cxcl10...
  57. Pankratova E, Stepchenko A, Krylova I, Portseva T, Georgieva S. Involvement of transcription factor Oct-1 in the regulation of JAK-STAT signaling pathway in cells of Burkitt lymphoma. Dokl Biochem Biophys. 2016;468:229-31 pubmed publisher
    ..Oct-1X) causes a decrease in the activity of four genes involved in the JAK-STAT signaling pathway-IFNAR2, STAT1, STAT2, and STAT4...
  58. Sung P, Cheon H, Cho C, Hong S, Park D, Seo H, et al. Roles of unphosphorylated ISGF3 in HCV infection and interferon responsiveness. Proc Natl Acad Sci U S A. 2015;112:10443-8 pubmed publisher
    ..identified as a tripartite transcription factor formed by high levels of IFN response factor 9 (IRF9), STAT1, and STAT2 without tyrosine phosphorylation of the STATs...
  59. Ho J, Pelzel C, Begitt A, Mee M, Elsheikha H, Scott D, et al. STAT2 Is a Pervasive Cytokine Regulator due to Its Inhibition of STAT1 in Multiple Signaling Pathways. PLoS Biol. 2016;14:e2000117 pubmed publisher
    b>STAT2 is the quintessential transcription factor for type 1 interferons (IFNs), where it functions as a heterodimer with STAT1...
  60. Wu H, Liu J, Li G, Shen J, Huang Y. The transcriptional STAT3 is a potential target, whereas transcriptional STAT5A/5B/6 are new biomarkers for prognosis in human breast carcinoma. Oncotarget. 2017;8:36279-36288 pubmed publisher
    ..In survival analyses through the Kaplan-Meier plotter database, high transcription levels of STAT2/4/5A/5B/6 were associated with better relapse-free survival (RFS) in all BC patients...
  61. Parisien J, Lau J, Horvath C. STAT2 acts as a host range determinant for species-specific paramyxovirus interferon antagonism and simian virus 5 replication. J Virol. 2002;76:6435-41 pubmed
    ..degradation of cellular IFN-alpha/beta-activated signal transducers and activators of transcription STAT1 and STAT2. SV5 infection induces STAT1 degradation and IFN-alpha/beta inhibition efficiently in human cells but not in mouse ..
  62. Perez J, Fernando C, Nosach R, Huang Y, Harding J, Hill J. In vitro attenuation of a virulent swine isolate of Brachyspira hampsonii. Pathog Dis. 2018;76: pubmed publisher
    ..The resulting strain, P113, did not differ from P13 in terms of diagnostic biochemical characteristics but had an enhanced growth rate in ..
  63. Mowen K, David M. Role of the STAT1-SH2 domain and STAT2 in the activation and nuclear translocation of STAT1. J Biol Chem. 1998;273:30073-6 pubmed
    ..In addition, STAT2 is activated by IFNalpha, and, together with STAT1 and p48/ISGF3gamma, forms the transcription factor complex ..
  64. Saleh A, Nguyen V, Krolewski J. Affinity of Stat2 for the subunits of the interferon alpha receptor. Biochemistry. 2002;41:11261-8 pubmed
    ..phosphorylation of tyrosine 466 on IFNaR1, which in turn binds the SH2 domain of the latent transcription factor Stat2 to initiate signaling. Stat2 also binds to IFNaR2 in a constitutive, phosphorylation-independent manner...
  65. Precious B, Childs K, Fitzpatrick Swallow V, Goodbourn S, Randall R. Simian virus 5 V protein acts as an adaptor, linking DDB1 to STAT2, to facilitate the ubiquitination of STAT1. J Virol. 2005;79:13434-41 pubmed
    ..that while the SV5 V protein fails to bind to STAT1 directly, it binds directly and independently to both DDB1 and STAT2, two cellular proteins known to be essential for SV5-mediated degradation of STAT1...
  66. Fortunato G, Calcagno G, Bresciamorra V, Salvatore E, Filla A, Capone S, et al. Multiple sclerosis and hepatitis C virus infection are associated with single nucleotide polymorphisms in interferon pathway genes. J Interferon Cytokine Res. 2008;28:141-52 pubmed publisher
    ..35 SNPs studied, 3 were in IFN-alpha receptor (IFNAR-1), 10 in IFN-alpha/beta receptor (IFNAR-2), 9 in Stat1, 5 in Stat2, and 8 in IFN regulatory factor-1 (IRF-1)...
  67. Ramachandran A, Parisien J, Horvath C. STAT2 is a primary target for measles virus V protein-mediated alpha/beta interferon signaling inhibition. J Virol. 2008;82:8330-8 pubmed publisher
    ..signaling through protein interactions with signal transducer and activator of transcription proteins STAT1 and STAT2. Here we demonstrate that although STAT1 interference results from protein interactions within a V protein N-..
  68. Le V, Trilling M, Wilborn M, Hengel H, Zimmermann A. Human cytomegalovirus interferes with signal transducer and activator of transcription (STAT) 2 protein stability and tyrosine phosphorylation. J Gen Virol. 2008;89:2416-26 pubmed publisher
    ..of transcription (STAT) 2 during human cytomegalovirus (HCMV) replication and found that protein levels of STAT2 are downregulated...
  69. Kadeppagari R, Sanchez R, Foster T. HSV-2 inhibits type-I interferon signaling via multiple complementary and compensatory STAT2-associated mechanisms. Virus Res. 2012;167:273-84 pubmed publisher
    ..HSV-2 was found to completely abolish type-1 IFN-mediated signaling via multiple STAT2-associated mechanisms...
  70. Sugiyama T, Nishio Y, Kishimoto T, Akira S. Identification of alternative splicing form of Stat2. FEBS Lett. 1996;381:191-4 pubmed
    We identified alternatively spliced forms of Stat2 in human and mouse mRNAs. The spliced forms are generated by reading through the intron between exon 20 and 21, which correspond to the region encoding SH2 domain...
  71. Gupta S, Yan H, Wong L, Ralph S, Krolewski J, Schindler C. The SH2 domains of Stat1 and Stat2 mediate multiple interactions in the transduction of IFN-alpha signals. EMBO J. 1996;15:1075-84 pubmed
    ..members of the STAT (Signal Transducers and Activators of Transcription) family of signaling proteins, Stat1 and Stat2. Sequence comparison of these STATs has determined that they share several conserved domains, the most notable of ..
  72. Dumler I, Kopmann A, Wagner K, Mayboroda O, Jerke U, Dietz R, et al. Urokinase induces activation and formation of Stat4 and Stat1-Stat2 complexes in human vascular smooth muscle cells. J Biol Chem. 1999;274:24059-65 pubmed
    ..In this study, we demonstrate that Stat4 and Stat2, but not Stat3, Stat5, or Stat6, are rapidly activated in response to uPA...
  73. Liu W, Wang X, Mokhonov V, Shi P, Randall R, Khromykh A. Inhibition of interferon signaling by the New York 99 strain and Kunjin subtype of West Nile virus involves blockage of STAT1 and STAT2 activation by nonstructural proteins. J Virol. 2005;79:1934-42 pubmed publisher
    ..In addition, the phosphorylation of STAT2 and its translocation to the nucleus were also blocked by KUN, NY99, and their replicons in response to treatment ..
  74. Laver T, Nozell S, Benveniste E. IFN-beta-mediated inhibition of IL-8 expression requires the ISGF3 components Stat1, Stat2, and IRF-9. J Interferon Cytokine Res. 2008;28:13-23 pubmed publisher
    ..conclude, through use of cell lines deficient for ISGF3 components, that all three members of this complex, Stat1, Stat2, and IFN regulatory factor-9 (IRF-9), are required for IFN-beta-mediated inhibition of IL-8 expression...
  75. Xin Z, Han W, Zhao Z, Xia Q, Yin B, Yuan J, et al. PCBP2 enhances the antiviral activity of IFN-? against HCV by stabilizing the mRNA of STAT1 and STAT2. PLoS ONE. 2011;6:e25419 pubmed publisher
    ..RIP-qRT-PCR and RNA half-life further revealed that PCBP2 stabilizes the mRNA of STAT1 and STAT2 through binding the 3'Untranslated Region (UTR) of these two molecules, which are pivotal for the IFN-? anti-HCV ..
  76. Steen H, Nogusa S, Thapa R, Basagoudanavar S, Gill A, Merali S, et al. Identification of STAT2 serine 287 as a novel regulatory phosphorylation site in type I interferon-induced cellular responses. J Biol Chem. 2013;288:747-58 pubmed publisher
    b>STAT2 is a positive modulator of the transcriptional response to type I interferons (IFNs). STAT2 acquires transcriptional function by becoming tyrosine phosphorylated and imported to the nucleus following type I IFN receptor activation...
  77. Del Corno M, Donninelli G, Varano B, Da Sacco L, Masotti A, Gessani S. HIV-1 gp120 activates the STAT3/interleukin-6 axis in primary human monocyte-derived dendritic cells. J Virol. 2014;88:11045-55 pubmed publisher
    ..Thus, the identification of this transcription factor as a signaling molecule mediating some of gp120's biological effects unveils a new mechanism by which HIV-1 may deregulate DC functions and contribute to AIDS pathogenesis. ..
  78. George C, Samuel C. STAT2-dependent induction of RNA adenosine deaminase ADAR1 by type I interferon differs between mouse and human cells in the requirement for STAT1. Virology. 2015;485:363-70 pubmed publisher
    ..We show using Stat1(-/-), Stat2(-/-) and IRF9(-/-) MEFs that induction of ADAR1 p150 occurs by STAT2- and IRF9-dependent signaling that is ..
  79. Wichit S, Diop F, Hamel R, Talignani L, Ferraris P, Cornelie S, et al. Aedes Aegypti saliva enhances chikungunya virus replication in human skin fibroblasts via inhibition of the type I interferon signaling pathway. Infect Genet Evol. 2017;55:68-70 pubmed publisher
    ..Moreover, Western blotting analysis revealed that STAT2 and its phosphorylated form were down-regulated in the presence of mosquito saliva...
  80. Song F, Zhao L, Zhu R, Song Q, Deng J, Tian R, et al. Protective effect of an alpha 7 nicotinic acetylcholine receptor agonist against enterovirus 71 infection in neuronal cells. Antiviral Res. 2018;149:106-112 pubmed publisher
    ..RNA replication, and that increased levels of INF mRNA and its downstream antiviral proteins stimulated by the JAK-STAT2 pathway may contribute to the antiviral effect of PNU-282987...
  81. Qin J, Kamarashev J, Zhang C, Dummer R, Burg G, Dobbeling U. Constitutive and interleukin-7- and interleukin-15-stimulated DNA binding of STAT and novel factors in cutaneous T cell lymphoma cells. J Invest Dermatol. 2001;117:583-9 pubmed
    On testing cutaneous T cell lymphoma cell lines and skin lesions, we found that the transcription factors STAT2, STAT3, STAT5, and STAT6 (STAT, signal transducer and activator of transcription) were present in the nuclei of these cells ..
  82. Wesoly J, Szweykowska Kulinska Z, Bluyssen H. STAT activation and differential complex formation dictate selectivity of interferon responses. Acta Biochim Pol. 2007;54:27-38 pubmed
    ..In addition, the fact that STAT2 homodimers are not capable of binding consensus GAS sites leaves the possibility for a novel type of DNA-binding ..
  83. Caignard G, Bouraï M, Jacob Y, Tangy F, Vidalain P. Inhibition of IFN-alpha/beta signaling by two discrete peptides within measles virus V protein that specifically bind STAT1 and STAT2. Virology. 2009;383:112-20 pubmed publisher
    ..Here we report a direct interaction between the VCT of MV-V and STAT2, a third component of IFN-alpha/beta transduction machinery...
  84. Kim S, Lee C. Counter-regulation mechanism of IL-4 and IFN-? signal transduction through cytosolic retention of the pY-STAT6:pY-STAT2:p48 complex. Eur J Immunol. 2011;41:461-72 pubmed publisher
    ..we demonstrated the colocalization and molecular interaction of IL-4-induced pY-STAT6 with IFN-?-induced pY-STAT2:p48 in the cytosol...
  85. Cheon H, Holvey Bates E, Schoggins J, Forster S, Hertzog P, Imanaka N, et al. IFN?-dependent increases in STAT1, STAT2, and IRF9 mediate resistance to viruses and DNA damage. EMBO J. 2013;32:2751-63 pubmed publisher
  86. Blaszczyk K, Nowicka H, Kostyrko K, Antonczyk A, Wesoly J, Bluyssen H. The unique role of STAT2 in constitutive and IFN-induced transcription and antiviral responses. Cytokine Growth Factor Rev. 2016;29:71-81 pubmed publisher
    In the canonical pathway of IFN-I-mediated signaling, phosphorylation of STAT1 and STAT2 leads to heterodimerization and interaction with IRF9...
  87. Nair S, Bist P, Dikshit N, Krishnan M. Global functional profiling of human ubiquitome identifies E3 ubiquitin ligase DCST1 as a novel negative regulator of Type-I interferon signaling. Sci Rep. 2016;6:36179 pubmed publisher
    ..regulated Type I interferon signaling by interacting with and promoting ubiquitination-mediated degradation of STAT2, an essential component of antiviral gene induction...
  88. Zhu X, Wang D, Zhou J, Pan T, Chen J, Yang Y, et al. Porcine Deltacoronavirus nsp5 Antagonizes Type I Interferon Signaling by Cleaving STAT2. J Virol. 2017;91: pubmed publisher
    ..Detailed analysis showed that nsp5 cleaved signal transducer and activator of transcription 2 (STAT2) but not Janus kinase 1 (JAK1), tyrosine kinase 2 (TYK2), STAT1, and interferon ..
  89. Liu S, Jiang M, Wang W, Liu W, Song X, Ma Z, et al. Nuclear RNF2 inhibits interferon function by promoting K33-linked STAT1 disassociation from DNA. Nat Immunol. 2018;19:41-52 pubmed publisher
    ..of the DNA-binding domain of STAT1 at position K379, in addition to promoting the disassociation of STAT1/STAT2 from DNA and consequently suppressing ISG transcription...
  90. Brzózka K, Finke S, Conzelmann K. Inhibition of interferon signaling by rabies virus phosphoprotein P: activation-dependent binding of STAT1 and STAT2. J Virol. 2006;80:2675-83 pubmed
    ..IFN-mediated tyrosine phosphorylation of STAT1 and STAT2 was not impaired in RV P-expressing cells; rather, a defect in STAT recycling was suggested by distinct ..
  91. Brierley M, Marchington K, Jurisica I, Fish E. Identification of GAS-dependent interferon-sensitive target genes whose transcription is STAT2-dependent but ISGF3-independent. FEBS J. 2006;273:1569-81 pubmed
    b>Signal transducer and activator of transcription 2 (STAT2) is best known as a critical transactivator component of the interferon-stimulated gene factor 3 (ISGF3) complex that drives the expression of many interferon (IFN)-inducible genes...
  92. Zhao D, Yan T, Li L, You S, Zhang C. Respiratory syncytial virus inhibits interferon-alpha-inducible signaling in macrophage-like U937 cells. J Infect. 2007;54:393-8 pubmed
    ..and phosphorylation of the IFN-alpha-inducible signal transducer and activator of transcription (STAT1 and STAT2) was suppressed...