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Signal transducer and activator of transcription 1, 91kDa

STAT1 bound to DNA
Available structures
1bf5, 1yvl
Identifiers
Symbols STAT1; DKFZp686B04100; ISGF-3; STAT91
External IDs OMIM600555 MGI103063 HomoloGene21428 GeneCards: STAT1 Gene
RNA expression pattern
PBB GE STAT1 200887 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 6772 20846
Ensembl ENSG00000115415 ENSMUSG00000026104
UniProt P42224 Q3TW11
RefSeq (mRNA) NM_007315 NM_009283
RefSeq (protein) NP_009330 NP_033309
Location (UCSC) Chr 2:
191.54 - 191.59 Mb
Chr 1:
52.07 - 52.1 Mb
PubMed search [1] [2]

STAT1 is a member of the Signal Transducers and Activators of Transcription family of transcription factors. STAT1 is involved in upregulating genes due to a signal by either type I or type II interferons. In response to IFN-γ stimulation, STAT1 forms homodimers or heterodimers with STAT3 that bind to the GAS (Interferon-Gamma Activated Sequence) promoter element; in response to either IFN-α or IFN-β stimulation, STAT1 forms a heterodimer with STAT2 that can bind the ISRE (Interferon Stimulated Response Element) promoter element.[1] In either case, binding of the promoter element leads to an increased expression of ISG (Interferon Stimulated Genes).

Expression of STAT1 can be induced with diallyl disulfide, a compound in garlic.[2]

Interactions

STAT1 has been shown to interact with Protein kinase R,[3][4] Src,[5][6] IRF1,[7] STAT3,[8][9][10] MCM5,[11][12] STAT2,[13][14][15] CD117,[16] Fanconi anemia, complementation group C,[17][18][19] CREB binding protein,[20] Interleukin 27 receptor, alpha subunit,[21] PIAS1,[22] BRCA1,[23] Epidermal growth factor receptor,[5][10] PTK2,[24] Mammalian target of rapamycin,[25] IFNAR2,[26][27] PRKCD,[25] TRADD,[28] C-jun,[29] Calcitriol receptor,[30] ISGF3G[31] and GNB2L1.[32][27]

References

  1. ^ Michael G. Katze, Yupeng He & Michael Gale, et al. (2002). "Viruses and interferon: a fight for supremacy.". Nature Reviews Immunology 2 (9): 675–87. doi:10.1038/nri888. PMID 12209136.  
  2. ^ Lu HF, Yang JS, Lin YT, Tan TW, Ip SW, Li YC, Tsou MF, Chung JG. (2007). "Diallyl disulfide induced signal transducer and activator of transcription 1 expression in human colon cancer colo 205 cells using differential display RT-PCR.". Cancer Genomics Proteomics. 4 (2): 93–97. PMID 17804871.  
  3. ^ Wong, A H; Tam N W, Yang Y L, Cuddihy A R, Li S, Kirchhoff S, Hauser H, Decker T, Koromilas A E (Mar. 1997). "Physical association between STAT1 and the interferon-inducible protein kinase PKR and implications for interferon and double-stranded RNA signaling pathways". EMBO J. (ENGLAND) 16 (6): 1291–304. doi:10.1093/emboj/16.6.1291. ISSN 0261-4189. PMID 9135145.  
  4. ^ Wong, A H; Durbin J E, Li S, Dever T E, Decker T, Koromilas A E (Apr. 2001). "Enhanced antiviral and antiproliferative properties of a STAT1 mutant unable to interact with the protein kinase PKR". J. Biol. Chem. (United States) 276 (17): 13727–37. doi:10.1074/jbc.M011240200. ISSN 0021-9258. PMID 11278865.  
  5. ^ a b Olayioye, M A; Beuvink I, Horsch K, Daly J M, Hynes N E (Jun. 1999). "ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases". J. Biol. Chem. (UNITED STATES) 274 (24): 17209–18. ISSN 0021-9258. PMID 10358079.  
  6. ^ Cirri, P; Chiarugi P, Marra F, Raugei G, Camici G, Manao G, Ramponi G (Oct. 1997). "c-Src activates both STAT1 and STAT3 in PDGF-stimulated NIH3T3 cells". Biochem. Biophys. Res. Commun. (UNITED STATES) 239 (2): 493–7. doi:10.1006/bbrc.1997.7493. ISSN 0006-291X. PMID 9344858.  
  7. ^ Chatterjee-Kishore, M; van Den Akker F, Stark G R (Jul. 2000). "Adenovirus E1A down-regulates LMP2 transcription by interfering with the binding of stat1 to IRF1". J. Biol. Chem. (UNITED STATES) 275 (27): 20406–11. doi:10.1074/jbc.M001861200. ISSN 0021-9258. PMID 10764778.  
  8. ^ Gunaje, J J; Bhat G J (Oct. 2001). "Involvement of tyrosine phosphatase PTP1D in the inhibition of interleukin-6-induced Stat3 signaling by alpha-thrombin". Biochem. Biophys. Res. Commun. (United States) 288 (1): 252–7. doi:10.1006/bbrc.2001.5759. ISSN 0006-291X. PMID 11594781.  
  9. ^ Spiekermann, K; Biethahn S, Wilde S, Hiddemann W, Alves F (Aug. 2001). "Constitutive activation of STAT transcription factors in acute myelogenous leukemia". Eur. J. Haematol. (Denmark) 67 (2): 63–71. ISSN 0902-4441. PMID 11722592.  
  10. ^ a b Xia, Ling; Wang Lijuan, Chung Alicia S, Ivanov Stanimir S, Ling Mike Y, Dragoi Ana M, Platt Adam, Gilmer Tona M, Fu Xin-Yuan, Chin Y Eugene (Aug. 2002). "Identification of both positive and negative domains within the epidermal growth factor receptor COOH-terminal region for signal transducer and activator of transcription (STAT) activation". J. Biol. Chem. (United States) 277 (34): 30716–23. doi:10.1074/jbc.M202823200. ISSN 0021-9258. PMID 12070153.  
  11. ^ Zhang, J J; Zhao Y, Chait B T, Lathem W W, Ritzi M, Knippers R, Darnell J E (Dec. 1998). "Ser727-dependent recruitment of MCM5 by Stat1alpha in IFN-gamma-induced transcriptional activation". EMBO J. (ENGLAND) 17 (23): 6963–71. doi:10.1093/emboj/17.23.6963. ISSN 0261-4189. PMID 9843502.  
  12. ^ DaFonseca, C J; Shu F, Zhang J J (Mar. 2001). "Identification of two residues in MCM5 critical for the assembly of MCM complexes and Stat1-mediated transcription activation in response to IFN-gamma". Proc. Natl. Acad. Sci. U.S.A. (United States) 98 (6): 3034–9. doi:10.1073/pnas.061487598. ISSN 0027-8424. PMID 11248027.  
  13. ^ Li, X; Leung S, Qureshi S, Darnell J E, Stark G R (Mar. 1996). "Formation of STAT1-STAT2 heterodimers and their role in the activation of IRF-1 gene transcription by interferon-alpha". J. Biol. Chem. (UNITED STATES) 271 (10): 5790–4. ISSN 0021-9258. PMID 8621447.  
  14. ^ Dumler, I; Kopmann A, Wagner K, Mayboroda O A, Jerke U, Dietz R, Haller H, Gulba D C (Aug. 1999). "Urokinase induces activation and formation of Stat4 and Stat1-Stat2 complexes in human vascular smooth muscle cells". J. Biol. Chem. (UNITED STATES) 274 (34): 24059–65. ISSN 0021-9258. PMID 10446176.  
  15. ^ Fagerlund, Riku; Mélen Krister, Kinnunen Leena, Julkunen Ilkka (Aug. 2002). "Arginine/lysine-rich nuclear localization signals mediate interactions between dimeric STATs and importin alpha 5". J. Biol. Chem. (United States) 277 (33): 30072–8. doi:10.1074/jbc.M202943200. ISSN 0021-9258. PMID 12048190.  
  16. ^ Deberry, C; Mou S, Linnekin D (Oct. 1997). "Stat1 associates with c-kit and is activated in response to stem cell factor". Biochem. J. (ENGLAND) 327 ( Pt 1): 73–80. ISSN 0264-6021. PMID 9355737.  
  17. ^ Pang, Q; Fagerlie S, Christianson T A, Keeble W, Faulkner G, Diaz J, Rathbun R K, Bagby G C (Jul. 2000). "The Fanconi anemia protein FANCC binds to and facilitates the activation of STAT1 by gamma interferon and hematopoietic growth factors". Mol. Cell. Biol. (UNITED STATES) 20 (13): 4724–35. ISSN 0270-7306. PMID 10848598.  
  18. ^ Reuter, Tanja Y; Medhurst Annette L, Waisfisz Quinten, Zhi Yu, Herterich Sabine, Hoehn Holger, Gross Hans J, Joenje Hans, Hoatlin Maureen E, Mathew Christopher G, Huber Pia A J (Oct. 2003). "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport". Exp. Cell Res. (United States) 289 (2): 211–21. ISSN 0014-4827. PMID 14499622.  
  19. ^ Pang, Q; Christianson T A, Keeble W, Diaz J, Faulkner G R, Reifsteck C, Olson S, Bagby G C (Sep. 2001). "The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality". Blood (United States) 98 (5): 1392–401. ISSN 0006-4971. PMID 11520787.  
  20. ^ Zhang, J J; Vinkemeier U, Gu W, Chakravarti D, Horvath C M, Darnell J E (Dec. 1996). "Two contact regions between Stat1 and CBP/p300 in interferon gamma signaling". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 93 (26): 15092–6. ISSN 0027-8424. PMID 8986769.  
  21. ^ Takeda, Atsunobu; Hamano Shinjiro, Yamanaka Atsushi, Hanada Toshikatsu, Ishibashi Tatsuro, Mak Tak W, Yoshimura Akihiko, Yoshida Hiroki (May. 2003). "Cutting edge: role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment". J. Immunol. (United States) 170 (10): 4886–90. ISSN 0022-1767. PMID 12734330.  
  22. ^ Liao, J; Fu Y, Shuai K (May. 2000). "Distinct roles of the NH2- and COOH-terminal domains of the protein inhibitor of activated signal transducer and activator of transcription (STAT) 1 (PIAS1) in cytokine-induced PIAS1-Stat1 interaction". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (10): 5267–72. ISSN 0027-8424. PMID 10805787.  
  23. ^ Ouchi, T; Lee S W, Ouchi M, Aaronson S A, Horvath C M (May. 2000). "Collaboration of signal transducer and activator of transcription 1 (STAT1) and BRCA1 in differential regulation of IFN-gamma target genes". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (10): 5208–13. doi:10.1073/pnas.080469697. ISSN 0027-8424. PMID 10792030.  
  24. ^ Xie, B; Zhao J, Kitagawa M, Durbin J, Madri J A, Guan J L, Fu X Y (Jun. 2001). "Focal adhesion kinase activates Stat1 in integrin-mediated cell migration and adhesion". J. Biol. Chem. (United States) 276 (22): 19512–23. doi:10.1074/jbc.M009063200. ISSN 0021-9258. PMID 11278462.  
  25. ^ a b Kristof, Arnold S; Marks-Konczalik Joanna, Billings Eric, Moss Joel (Sep. 2003). "Stimulation of signal transducer and activator of transcription-1 (STAT1)-dependent gene transcription by lipopolysaccharide and interferon-gamma is regulated by mammalian target of rapamycin". J. Biol. Chem. (United States) 278 (36): 33637–44. doi:10.1074/jbc.M301053200. ISSN 0021-9258. PMID 12807916.  
  26. ^ Li, X; Leung S, Kerr I M, Stark G R (Apr. 1997). "Functional subdomains of STAT2 required for preassociation with the alpha interferon receptor and for signaling". Mol. Cell. Biol. (UNITED STATES) 17 (4): 2048–56. ISSN 0270-7306. PMID 9121453.  
  27. ^ a b Usacheva, A; Smith R, Minshall R, Baida G, Seng S, Croze E, Colamonici O (Jun. 2001). "The WD motif-containing protein receptor for activated protein kinase C (RACK1) is required for recruitment and activation of signal transducer and activator of transcription 1 through the type I interferon receptor". J. Biol. Chem. (United States) 276 (25): 22948–53. doi:10.1074/jbc.M100087200. ISSN 0021-9258. PMID 11301323.  
  28. ^ Wang, Y; Wu T R, Cai S, Welte T, Chin Y E (Jul. 2000). "Stat1 as a component of tumor necrosis factor alpha receptor 1-TRADD signaling complex to inhibit NF-kappaB activation". Mol. Cell. Biol. (UNITED STATES) 20 (13): 4505–12. ISSN 0270-7306. PMID 10848577.  
  29. ^ Zhang, X; Wrzeszczynska M H, Horvath C M, Darnell J E (Oct. 1999). "Interacting regions in Stat3 and c-Jun that participate in cooperative transcriptional activation". Mol. Cell. Biol. (UNITED STATES) 19 (10): 7138–46. ISSN 0270-7306. PMID 10490649.  
  30. ^ Vidal, Marcos; Ramana Chilakamarti V, Dusso Adriana S (Apr. 2002). "Stat1-vitamin D receptor interactions antagonize 1,25-dihydroxyvitamin D transcriptional activity and enhance stat1-mediated transcription". Mol. Cell. Biol. (United States) 22 (8): 2777–87. ISSN 0270-7306. PMID 11909970.  
  31. ^ Horvath, C M; Stark G R, Kerr I M, Darnell J E (Dec. 1996). "Interactions between STAT and non-STAT proteins in the interferon-stimulated gene factor 3 transcription complex". Mol. Cell. Biol. (UNITED STATES) 16 (12): 6957–64. ISSN 0270-7306. PMID 8943351.  
  32. ^ Usacheva, Anna; Tian Xinyong, Sandoval Raudel, Salvi Debra, Levy David, Colamonici Oscar R (Sep. 2003). "The WD motif-containing protein RACK-1 functions as a scaffold protein within the type I IFN receptor-signaling complex". J. Immunol. (United States) 171 (6): 2989–94. ISSN 0022-1767. PMID 12960323.  

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