STAT1

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Signal transducer and activator of transcription 1, 91kDa
Stat1 stucture.png
STAT1 bound to DNA
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols STAT1 ; CANDF7; ISGF-3; STAT91
External IDs OMIM600555 MGI103063 HomoloGene21428 ChEMBL: 6101 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 P42225
RefSeq (mRNA) NM_007315 NM_001205313
RefSeq (protein) NP_009330 NP_001192242
Location (UCSC) Chr 2:
191.83 – 191.89 Mb
Chr 1:
52.12 – 52.16 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, type II, or type III 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[edit]

STAT1 has been shown to interact with:

References[edit]

  1. ^ Katze MG, He Y 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 et al. (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): 93–7. PMID 17804871. 
  3. ^ Ouchi T, Lee SW, Ouchi M, Aaronson SA, Horvath CM (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. 97 (10): 5208–13. doi:10.1073/pnas.080469697. PMC 25807. PMID 10792030. 
  4. ^ Zhang X, Wrzeszczynska MH, Horvath CM, Darnell JE (October 1999). "Interacting regions in Stat3 and c-Jun that participate in cooperative transcriptional activation". Mol. Cell. Biol. 19 (10): 7138–46. PMC 84707. PMID 10490649. 
  5. ^ Deberry C, Mou S, Linnekin D (October 1997). "Stat1 associates with c-kit and is activated in response to stem cell factor". Biochem. J. 327 (1): 73–80. PMC 1218765. PMID 9355737. 
  6. ^ Zhang JJ, Vinkemeier U, Gu W, Chakravarti D, Horvath CM, Darnell JE (Dec 1996). "Two contact regions between Stat1 and CBP/p300 in interferon gamma signaling". Proc. Natl. Acad. Sci. U.S.A. 93 (26): 15092–6. doi:10.1073/pnas.93.26.15092. PMC 26361. PMID 8986769. 
  7. ^ Vidal M, Ramana CV, Dusso AS (April 2002). "Stat1-vitamin D receptor interactions antagonize 1,25-dihydroxyvitamin D transcriptional activity and enhance stat1-mediated transcription". Mol. Cell. Biol. 22 (8): 2777–87. doi:10.1128/mcb.22.8.2777-2787.2002. PMC 133712. PMID 11909970. 
  8. ^ a b Olayioye MA, Beuvink I, Horsch K, Daly JM, Hynes NE (June 1999). "ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases". J. Biol. Chem. 274 (24): 17209–18. doi:10.1074/jbc.274.24.17209. PMID 10358079. 
  9. ^ a b Xia L, Wang L, Chung AS, Ivanov SS, Ling MY, Dragoi AM et al. (August 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. 277 (34): 30716–23. doi:10.1074/jbc.M202823200. PMID 12070153. 
  10. ^ Pang Q, Fagerlie S, Christianson TA, Keeble W, Faulkner G, Diaz J et al. (July 2000). "The Fanconi anemia protein FANCC binds to and facilitates the activation of STAT1 by gamma interferon and hematopoietic growth factors". Mol. Cell. Biol. 20 (13): 4724–35. doi:10.1128/mcb.20.13.4724-4735.2000. PMC 85895. PMID 10848598. 
  11. ^ Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H et al. (October 2003). "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport". Exp. Cell Res. 289 (2): 211–21. doi:10.1016/s0014-4827(03)00261-1. PMID 14499622. 
  12. ^ Pang Q, Christianson TA, Keeble W, Diaz J, Faulkner GR, Reifsteck C et al. (September 2001). "The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality". Blood 98 (5): 1392–401. doi:10.1182/blood.v98.5.1392. PMID 11520787. 
  13. ^ a b Usacheva A, Smith R, Minshall R, Baida G, Seng S, Croze E et al. (June 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. 276 (25): 22948–53. doi:10.1074/jbc.M100087200. PMID 11301323. 
  14. ^ Usacheva A, Tian X, Sandoval R, Salvi D, Levy D, Colamonici OR (September 2003). "The WD motif-containing protein RACK-1 functions as a scaffold protein within the type I IFN receptor-signaling complex". J. Immunol. 171 (6): 2989–94. doi:10.4049/jimmunol.171.6.2989. PMID 12960323. 
  15. ^ Li X, Leung S, Kerr IM, Stark GR (April 1997). "Functional subdomains of STAT2 required for preassociation with the alpha interferon receptor and for signaling". Mol. Cell. Biol. 17 (4): 2048–56. PMC 232052. PMID 9121453. 
  16. ^ Chatterjee-Kishore M, van Den Akker F, Stark GR (July 2000). "Adenovirus E1A down-regulates LMP2 transcription by interfering with the binding of stat1 to IRF1". J. Biol. Chem. 275 (27): 20406–11. doi:10.1074/jbc.M001861200. PMID 10764778. 
  17. ^ Horvath CM, Stark GR, Kerr IM, Darnell JE (Dec 1996). "Interactions between STAT and non-STAT proteins in the interferon-stimulated gene factor 3 transcription complex". Mol. Cell. Biol. 16 (12): 6957–64. PMC 231699. PMID 8943351. 
  18. ^ Takeda A, Hamano S, Yamanaka A, Hanada T, Ishibashi T, Mak TW et al. (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. 170 (10): 4886–90. doi:10.4049/jimmunol.170.10.4886. PMID 12734330. 
  19. ^ Zhang JJ, Zhao Y, Chait BT, Lathem WW, Ritzi M, Knippers R et al. (Dec 1998). "Ser727-dependent recruitment of MCM5 by Stat1alpha in IFN-gamma-induced transcriptional activation". EMBO J. 17 (23): 6963–71. doi:10.1093/emboj/17.23.6963. PMC 1171044. PMID 9843502. 
  20. ^ DaFonseca CJ, Shu F, Zhang JJ (March 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. 98 (6): 3034–9. doi:10.1073/pnas.061487598. PMC 30602. PMID 11248027. 
  21. ^ a b Kristof AS, Marks-Konczalik J, Billings E, Moss J (September 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. 278 (36): 33637–44. doi:10.1074/jbc.M301053200. PMID 12807916. 
  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. 97 (10): 5267–72. doi:10.1073/pnas.97.10.5267. PMC 25817. PMID 10805787. 
  23. ^ Xie B, Zhao J, Kitagawa M, Durbin J, Madri JA, Guan JL et al. (June 2001). "Focal adhesion kinase activates Stat1 in integrin-mediated cell migration and adhesion". J. Biol. Chem. 276 (22): 19512–23. doi:10.1074/jbc.M009063200. PMID 11278462. 
  24. ^ Wong AH, Tam NW, Yang YL, Cuddihy AR, Li S, Kirchhoff S et al. (March 1997). "Physical association between STAT1 and the interferon-inducible protein kinase PKR and implications for interferon and double-stranded RNA signaling pathways". EMBO J. 16 (6): 1291–304. doi:10.1093/emboj/16.6.1291. PMC 1169727. PMID 9135145. 
  25. ^ Wong AH, Durbin JE, Li S, Dever TE, Decker T, Koromilas AE (April 2001). "Enhanced antiviral and antiproliferative properties of a STAT1 mutant unable to interact with the protein kinase PKR". J. Biol. Chem. 276 (17): 13727–37. doi:10.1074/jbc.M011240200. PMID 11278865. 
  26. ^ Li X, Leung S, Qureshi S, Darnell JE, Stark GR (March 1996). "Formation of STAT1-STAT2 heterodimers and their role in the activation of IRF-1 gene transcription by interferon-alpha". J. Biol. Chem. 271 (10): 5790–4. doi:10.1074/jbc.271.10.5790. PMID 8621447. 
  27. ^ Dumler I, Kopmann A, Wagner K, Mayboroda OA, Jerke U, Dietz R et al. (August 1999). "Urokinase induces activation and formation of Stat4 and Stat1-Stat2 complexes in human vascular smooth muscle cells". J. Biol. Chem. 274 (34): 24059–65. doi:10.1074/jbc.274.34.24059. PMID 10446176. 
  28. ^ Fagerlund R, Mélen K, Kinnunen L, Julkunen I (August 2002). "Arginine/lysine-rich nuclear localization signals mediate interactions between dimeric STATs and importin alpha 5". J. Biol. Chem. 277 (33): 30072–8. doi:10.1074/jbc.M202943200. PMID 12048190.  Vancouver style error (help)
  29. ^ Gunaje JJ, Bhat GJ (October 2001). "Involvement of tyrosine phosphatase PTP1D in the inhibition of interleukin-6-induced Stat3 signaling by alpha-thrombin". Biochem. Biophys. Res. Commun. 288 (1): 252–7. doi:10.1006/bbrc.2001.5759. PMID 11594781. 
  30. ^ Spiekermann K, Biethahn S, Wilde S, Hiddemann W, Alves F (August 2001). "Constitutive activation of STAT transcription factors in acute myelogenous leukemia". Eur. J. Haematol. 67 (2): 63–71. doi:10.1034/j.1600-0609.2001.00385.x. PMID 11722592. 
  31. ^ Cirri P, Chiarugi P, Marra F, Raugei G, Camici G, Manao G et al. (October 1997). "c-Src activates both STAT1 and STAT3 in PDGF-stimulated NIH3T3 cells". Biochem. Biophys. Res. Commun. 239 (2): 493–7. doi:10.1006/bbrc.1997.7493. PMID 9344858. 
  32. ^ Wang Y, Wu TR, Cai S, Welte T, Chin YE (July 2000). "Stat1 as a component of tumor necrosis factor alpha receptor 1-TRADD signaling complex to inhibit NF-kappaB activation". Mol. Cell. Biol. 20 (13): 4505–12. doi:10.1128/mcb.20.13.4505-4512.2000. PMC 85828. PMID 10848577. 

Further reading[edit]

External links[edit]