STAT1

Signal transducer and activator of transcription 1, 91kDa
STAT1 bound to DNA
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1BF5​, 1YVL​, 2KA6​
Identifiers
Symbols	STAT1 ; CANDF7; IMD31A; IMD31B; IMD31C; ISGF-3; STAT91
External IDs	OMIM: 600555 MGI: 103063 HomoloGene: 21428 ChEMBL: 6101 GeneCards: STAT1 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • RNA polymerase II core promoter sequence-specific DNA binding • transcription factor activity, RNA polymerase II core promoter sequence-specific • double-stranded DNA binding • transcription factor activity, sequence-specific DNA binding • signal transducer activity • tumor necrosis factor receptor binding • protein binding • enzyme binding • identical protein binding • protein homodimerization activity Cellular component • nuclear chromatin • nucleus • nucleoplasm • nucleolus • cytoplasm • cytosol • axon • dendrite • perinuclear region of cytoplasm Biological process • negative regulation of transcription from RNA polymerase II promoter • negative regulation of endothelial cell proliferation • positive regulation of mesenchymal cell proliferation • negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis • transcription, DNA-templated • regulation of transcription from RNA polymerase II promoter • apoptotic process • JAK-STAT cascade • blood circulation • viral process • negative regulation of angiogenesis • cytokine-mediated signaling pathway • lipopolysaccharide-mediated signaling pathway • tumor necrosis factor-mediated signaling pathway • response to cytokine • negative regulation of macrophage fusion • response to interferon-beta • cellular response to interferon-beta • regulation of apoptotic process • negative regulation of I-kappaB kinase/NF-kappaB signaling • response to exogenous dsRNA • response to peptide hormone • endothelial cell migration • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • negative regulation by virus of viral protein levels in host cell • positive regulation of smooth muscle cell proliferation • response to cAMP • defense response to virus • interferon-gamma-mediated signaling pathway • regulation of interferon-gamma-mediated signaling pathway • type I interferon signaling pathway • regulation of type I interferon-mediated signaling pathway • JAK-STAT cascade involved in growth hormone signaling pathway • renal tubule development • metanephric mesenchymal cell proliferation involved in metanephros development • metanephric mesenchymal cell differentiation • negative regulation of metanephric nephron tubule epithelial cell differentiation Sources: Amigo / QuickGO
RNA expression pattern
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: 190.96 – 191.02 Mb	Chr 1: 52.12 – 52.16 Mb
PubMed search

Signal transducer and activator of transcription 1 (STAT1) is a transcription factor which in humans is encoded by the STAT1 gene. It is a member of the STAT protein family.

Function

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

STAT1 has been shown to interact with:

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

References

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, 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): 93–7. 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. 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. Xia L, Wang L, Chung AS, Ivanov SS, Ling MY, Dragoi AM, Platt A, Gilmer TM, Fu XY, Chin YE (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, Rathbun RK, Bagby GC (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, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA (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, Olson S, Bagby GC (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. Usacheva A, Smith R, Minshall R, Baida G, Seng S, Croze E, Colamonici O (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, Yoshimura A, Yoshida H (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, Darnell JE (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. 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, Fu XY (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, Hauser H, Decker T, Koromilas AE (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, Haller H, Gulba DC (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.
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.t01-1-00385.x. PMID 11722592.
31. Cirri P, Chiarugi P, Marra F, Raugei G, Camici G, Manao G, Ramponi G (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

• Cebulla CM, Miller DM, Sedmak DD (2000). "Viral inhibition of interferon signal transduction". Intervirology 42 (5–6): 325–30. doi:10.1159/000053968. PMID 10702714.
• Kisseleva T, Bhattacharya S, Braunstein J, Schindler CW (2002). "Signaling through the JAK/STAT pathway, recent advances and future challenges". Gene 285 (1–2): 1–24. doi:10.1016/S0378-1119(02)00398-0. PMID 12039028.
• Joseph AM, Kumar M, Mitra D (2005). "Nef: "necessary and enforcing factor" in HIV infection". Curr. HIV Res. 3 (1): 87–94. doi:10.2174/1570162052773013. PMID 15638726.

External links

• FactorBook STAT1