• regulation of apoptotic process • metanephric mesenchymal cell proliferation involved in metanephros development • regulation of transcription, DNA-templated • cellular response to interferon-beta • regulation of transcription by RNA polymerase II • negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis • metanephric mesenchymal cell differentiation • tumor necrosis factor-mediated signaling pathway • negative regulation of transcription by RNA polymerase II • renal tubule development • response to interferon-beta • negative regulation of I-kappaB kinase/NF-kappaB signaling • transcription, DNA-templated • negative regulation of endothelial cell proliferation • regulation of type I interferon-mediated signaling pathway • regulation of interferon-gamma-mediated signaling pathway • positive regulation of mesenchymal cell proliferation • negative regulation of metanephric nephron tubule epithelial cell differentiation • negative regulation of angiogenesis • negative regulation by virus of viral protein levels in host cell • GO:0022415 viral process • endothelial cell migration • positive regulation of transcription by RNA polymerase II • signal transduction • macrophage derived foam cell differentiation • positive regulation of erythrocyte differentiation • type I interferon signaling pathway • cellular response to interferon-gamma • positive regulation of defense response to virus by host • positive regulation of interferon-alpha production • positive regulation of transcription, DNA-templated • defense response to virus • interferon-gamma-mediated signaling pathway • receptor signaling pathway via JAK-STAT • response to nutrient • blood circulation • positive regulation of cell population proliferation • response to mechanical stimulus • response to organic cyclic compound • cellular response to insulin stimulus • response to cytokine • response to drug • response to hydrogen peroxide • response to peptide hormone • positive regulation of smooth muscle cell proliferation • response to cAMP • positive regulation of nitric-oxide synthase biosynthetic process • cellular response to cytokine stimulus • cellular response to organic cyclic compound • positive regulation of transcription of Notch receptor target • cytokine-mediated signaling pathway • interleukin-21-mediated signaling pathway • interleukin-6-mediated signaling pathway • interleukin-27-mediated signaling pathway • interleukin-35-mediated signaling pathway • interleukin-9-mediated signaling pathway • defense response • regulation of cell population proliferation
Sources:Amigo / QuickGO
Orthologs
Species
Human
Mouse
Entrez
6772
20846
Ensembl
ENSG00000115415
ENSMUSG00000026104
UniProt
P42224
P42225
RefSeq (mRNA)
NM_007315 NM_139266
NM_001205313 NM_001205314 NM_009283 NM_001357627
RefSeq (protein)
NP_009330 NP_644671
n/a
Location (UCSC)
Chr 2: 190.91 – 191.02 Mb
Chr 1: 52.12 – 52.16 Mb
PubMed search
[3]
[4]
Wikidata
View/Edit Human
View/Edit Mouse
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.
Contents
1 Function
1.1 Mutations of STAT1
1.1.1 Loss of function
1.1.2 Gain of function
2 Interactions
3 References
4 Further reading
5 External links
Function[edit]
All STAT molecules are phosphorylated by receptor associated kinases, that causes activation, dimerization by forming homo- or heterodimers and finally translocate to nucleus to work as transcription factors. Specifically STAT1 can be activated by several ligands such as Interferon alpha (IFNα), Interferon gamma (IFNγ), Epidermal Growth Factor (EGF), Platelet Derived Growαth Factor (PDGF), Interleukin 6 (IL-6), or IL-27 [5]
Type I interferons (IFN-α, IFN-ß) bind to receptors, cause signaling via kinases, phosphorylate and activate the Jak kinases TYK2 and JAK1 and also STAT1 and STAT2. STAT molecules form dimers and bind to ISGF3G/IRF-9, which is Interferon stimulated gene factor 3 complex with Interferon regulatory Factor 9. This allows STAT1 to enter the nucleus.[6] STAT1 has a key role in many gene expressions that cause survival of the cell, viability or pathogen response. There are two possible transcripts (due to alternative splicing) that encode 2 isoforms of STAT1[7][8]
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.[9] 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.[10]
Mutations of STAT1[edit]
Mutations in the STAT1 molecule can be gain of function (GOF) or loss of function (LOF). Both of them can cause different phenotypes and symptoms. Recurring common infections are frequent in both GOF and LOF mutations. In humans STAT1 has been particularly under strong purifying selection when populations shifted from hunting and gathering to farming, because this went along with a change in the pathogen spectrum.[11]
Loss of function[edit]
STAT1 loss of function, therefore STAT1 deficiency can have many variants. There are two main genetic impairments that can cause response to interferons type I and III. First there can be autosomal recessive partial or even complete deficiency of STAT1. That causes intracellular bacterial diseases or viral infections and impaired IFN a, b, g and IL27 responses are diagnosed. In partial form there can also be found high levels of IFNg in blood serum. When tested from whole blood, monocytes do not respond to BCG and IFNg doses with IL-12 production. In complete recessive form there is a very low response to anti-viral and antimycotical medication. Second, partial STAT1 deficiency can also be an autosomal dominant mutation; phenotypically causing impaired IFNg responses and causing patients to suffer with selective intracellular bacterial diseases (MSMD)[12]
In knock-out mice prepared in the 90s, a low amount of CD4+ and CD25+ regulatory T-cells and almost no IFNa, b and g response was discovered, which lead to parasital, viral and bacterial infections. The very first reported case of STAT1 deficiency in human was an autosomal dominant mutation and patients were showing propensity to mycobacterial infections.[7] Another case reported was about an autosomal recessive form. 2 related patients had a homozygous missense STAT1 mutation which caused impaired splicing, therefore a defect in mature protein. Patients had partially damaged response to both IFNa and IFNg. Scientists now claim that recessive STAT1 deficiency is a new form of primary immunodeficiency and whenever a patient suffers sudden, severe and unexpected bacterial and viral infections, should be considered as potentially STAT1 deficient[13][14]
Interferons induce the formation of two transcriptional activators: gamma-activating factor (GAF) and interferon-stimulated gamma factor 3 (ISGF3). A natural heterozygous germline STAT1 mutation associated with susceptibility to mycobacterial but not viral disease was found in two unrelated patients with unexplained mycobacterial disease.[15] This mutation caused a loss of GAF and ISGF3 activation but was dominant for one cellular phenotype and recessive for the other. It impaired the nuclear accumulation of GAF but not of ISGF3 in cells stimulated by interferons, implying that the antimycobacterial but not the antiviral effects of human interferons are mediated by GAF. More recently, two patients have been identified with homozygous STAT-1 mutations who developed both post–BCG vaccination disseminated disease and lethal viral infections. The mutations in these patients caused a complete lack of STAT-1 and resulted in a lack of formation of both GAF and ISGF3.[16]
Gain of function[edit]
Gain of function mutation was first discovered in patients with chronic mucocutaneous candidiasis (CMC). This disease is characteristic with its symptoms as persistent infections of the skin, mucosae - oral or genital and nails infections caused by Candida, mostly Candida albicans. CMC may very often result from primary immunodeficiency. Patients with CMC often suffer also with bacterial infections (mostly Staphylococcus aureus), also with infections of the respiratory system and skin. In these patients we can also find viral infections caused mostly by Herpesviridae, that also affect the skin. The mycobacterial infections are often caused by Mycobacterium tuberculosis or environmental bacteria. Very common are also autoimmune symptoms like type 1 diabetes, cytopenia, regression of the thymus or systemic lupus erythematosus. When T-cell deficient, these autoimmune díseases are very common. CMC was also reported as a common symptom in patients with hyper immunoglobulin E syndrome (hyper-IgE) and with autoimmune polyendocrine syndrome type I. There was reported an interleukin 17A role, because of low levels of IL-17A producing T-cells in CMC patients.
With various genomic and genetic methods was discovered, that a heterozygous gain of function mutation of STAT1 is a cause of more than a half CMC cases. This mutation is caused by defect in the coiled-coil domain, domain that binds DNA, N-terminal domain or SH2 domain. Because of this there is increased phosphorylation because of impossible dephosphorylation in nucleus. These processes are dependent on cytokines like interferon alpha or beta, interferon gamma or interleukin 27. As mentioned above, low levels of interleukin 17A were observed, therefore impaired the Th17 polarization of the immune response.
Patients with STAT1 gain of function mutation and CMC poorly or not at all respond to treatment with azole drugs such as Fluconazole, Itraconazole or Posaconazole. Besides common viral and bacterial infections, these patients develop autoimmunities or even carcinomas. It is very complicated to find a treatment because of various symptoms and resistancies, inhibitors of JAK/STAT pathway such as Ruxolitinib are being tested and are a possible choice of treatment for these patients[17][5][18]
Interactions[edit]
STAT1 has been shown to interact with:
BRCA1,[19]
C-jun,[20]
CD117,[21]
CREB-binding protein,[22]
Calcitriol receptor,[23]
Epidermal growth factor receptor,[24][25]
Fanconi anemia, complementation group C,[26][27][28]
GNB2L1,[29][30]
IFNAR2,[29][31]
IRF1,[32]
ISGF3G[33]
Interleukin 27 receptor, alpha subunit,[34]
MCM5,[35][36]
Mammalian target of rapamycin,[37]
PIAS1,[38]
PRKCD,[37]
PTK2,[39]
Protein kinase R,[40][41]
STAT2,[42][43][44]
STAT3,[25][45][46]
Src,[24][47] and
TRADD.[48]
References[edit]
^ a b cGRCh38: Ensembl release 89: ENSG00000115415 - Ensembl, May 2017
^ a b cGRCm38: Ensembl release 89: ENSMUSG00000026104 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ a bBaris S, Alroqi F, Kiykim A, Karakoc-Aydiner E, Ogulur I, Ozen A, Charbonnier LM, Bakır M, Boztug K, Chatila TA, Barlan IB (October 2016). "Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1". Journal of Clinical Immunology. 36 (7): 641–8. doi:10.1007/s10875-016-0312-3. PMC 5556363. PMID 27379765.
^Database, GeneCards Human Gene. "IRF9 Gene - GeneCards | IRF9 Protein | IRF9 Antibody". www.genecards.org. Retrieved 2017-06-01.
^ a b"STAT1 - Signal transducer and activator of transcription 1-alpha/beta - Homo sapiens (Human) - STAT1 gene & protein". www.uniprot.org. Retrieved 2017-06-01.
^"STAT1 signal transducer and activator of transcription 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-06-01.
^Katze MG, He Y, Gale M (September 2002). "Viruses and interferon: a fight for supremacy". Nature Reviews. Immunology. 2 (9): 675–87. doi:10.1038/nri888. PMID 12209136. S2CID 32798777.
^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.
^Deschamps M, Laval G, Fagny M, Itan Y, Abel L, Casanova JL, et al. (January 2016). "Genomic Signatures of Selective Pressures and Introgression from Archaic Hominins at Human Innate Immunity Genes". American Journal of Human Genetics. 98 (1): 5–21. doi:10.1016/j.ajhg.2015.11.014. PMC 4716683. PMID 26748513.
^Rezaei N, Aghamohammadi A, Notarangelo LD (2016-11-30). Primary Immunodeficiency Diseases: Definition, Diagnosis, and Management. Springer. ISBN 9783662529096.
^Chapgier A, Kong XF, Boisson-Dupuis S, Jouanguy E, Averbuch D, Feinberg J, Zhang SY, Bustamante J, Vogt G, Lejeune J, Mayola E, de Beaucoudrey L, Abel L, Engelhard D, Casanova JL (June 2009). "A partial form of recessive STAT1 deficiency in humans". The Journal of Clinical Investigation. 119 (6): 1502–14. doi:10.1172/jci37083. PMC 2689115. PMID 19436109.
^"Defects of STAT1 in Human. Loss of Function exposes to Mycobacteria. Gain of Function exposes to Candida". www.asid.ma-gb. Retrieved 2017-06-01.
^Dupuis S, Dargemont C, Fieschi C, et al. Impairment of mycobacterial but not viral immunity by a germline human STAT1 mutation. Science. 2001;293(5528):300–303.
^Dupuis S, Jouanguy E, Al Hajjar S, et al. Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency. Nat Genet. 2003;33(3):388–391.
^Toubiana J, Okada S, Hiller J, Oleastro M, Lagos Gomez M, Aldave Becerra JC, Ouachée-Chardin M, Fouyssac F, Girisha KM, Etzioni A, Van Montfrans J, Camcioglu Y, Kerns LA, Belohradsky B, Blanche S, Bousfiha A, Rodriguez-Gallego C, Meyts I, Kisand K, Reichenbach J, Renner ED, Rosenzweig S, Grimbacher B, van de Veerdonk FL, Traidl-Hoffmann C, Picard C, Marodi L, Morio T, Kobayashi M, Lilic D, Milner JD, Holland S, Casanova JL, Puel A (June 2016). "Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype". Blood. 127 (25): 3154–64. doi:10.1182/blood-2015-11-679902. PMC 4920021. PMID 27114460.
^Dupuis S, Jouanguy E, Al-Hajjar S, Fieschi C, Al-Mohsen IZ, Al-Jumaah S, Yang K, Chapgier A, Eidenschenk C, Eid P, Al Ghonaium A, Tufenkeji H, Frayha H, Al-Gazlan S, Al-Rayes H, Schreiber RD, Gresser I, Casanova JL (March 2003). "Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency". Nature Genetics. 33 (3): 388–91. doi:10.1038/ng1097. PMID 12590259. S2CID 15983552.
^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". Proceedings of the National Academy of Sciences of the United States of America. 97 (10): 5208–13. Bibcode:2000PNAS...97.5208O. doi:10.1073/pnas.080469697. PMC 25807. PMID 10792030.
^Zhang X, Wrzeszczynska MH, Horvath CM, Darnell JE (October 1999). "Interacting regions in Stat3 and c-Jun that participate in cooperative transcriptional activation". Molecular and Cellular Biology. 19 (10): 7138–46. doi:10.1128/MCB.19.10.7138. PMC 84707. PMID 10490649.
^Deberry C, Mou S, Linnekin D (October 1997). "Stat1 associates with c-kit and is activated in response to stem cell factor". The Biochemical Journal. 327 (1): 73–80. doi:10.1042/bj3270073. PMC 1218765. PMID 9355737.
^Zhang JJ, Vinkemeier U, Gu W, Chakravarti D, Horvath CM, Darnell JE (December 1996). "Two contact regions between Stat1 and CBP/p300 in interferon gamma signaling". Proceedings of the National Academy of Sciences of the United States of America. 93 (26): 15092–6. Bibcode:1996PNAS...9315092Z. doi:10.1073/pnas.93.26.15092. PMC 26361. PMID 8986769.
^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". Molecular and Cellular Biology. 22 (8): 2777–87. doi:10.1128/mcb.22.8.2777-2787.2002. PMC 133712. PMID 11909970.
^ a bOlayioye 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". The Journal of Biological Chemistry. 274 (24): 17209–18. doi:10.1074/jbc.274.24.17209. PMID 10358079.
^ a bXia 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". The Journal of Biological Chemistry. 277 (34): 30716–23. doi:10.1074/jbc.M202823200. PMID 12070153.
^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". Molecular and Cellular Biology. 20 (13): 4724–35. doi:10.1128/mcb.20.13.4724-4735.2000. PMC 85895. PMID 10848598.
^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". Experimental Cell Research. 289 (2): 211–21. doi:10.1016/s0014-4827(03)00261-1. PMID 14499622.
^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.
^ a bUsacheva 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". The Journal of Biological Chemistry. 276 (25): 22948–53. doi:10.1074/jbc.M100087200. PMID 11301323.
^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". Journal of Immunology. 171 (6): 2989–94. doi:10.4049/jimmunol.171.6.2989. PMID 12960323.
^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". Molecular and Cellular Biology. 17 (4): 2048–56. doi:10.1128/mcb.17.4.2048. PMC 232052. PMID 9121453.
^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". The Journal of Biological Chemistry. 275 (27): 20406–11. doi:10.1074/jbc.M001861200. PMID 10764778.
^Horvath CM, Stark GR, Kerr IM, Darnell JE (December 1996). "Interactions between STAT and non-STAT proteins in the interferon-stimulated gene factor 3 transcription complex". Molecular and Cellular Biology. 16 (12): 6957–64. doi:10.1128/mcb.16.12.6957. PMC 231699. PMID 8943351.
^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". Journal of Immunology. 170 (10): 4886–90. doi:10.4049/jimmunol.170.10.4886. PMID 12734330.
^Zhang JJ, Zhao Y, Chait BT, Lathem WW, Ritzi M, Knippers R, Darnell JE (December 1998). "Ser727-dependent recruitment of MCM5 by Stat1alpha in IFN-gamma-induced transcriptional activation". The EMBO Journal. 17 (23): 6963–71. doi:10.1093/emboj/17.23.6963. PMC 1171044. PMID 9843502.
^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". Proceedings of the National Academy of Sciences of the United States of America. 98 (6): 3034–9. Bibcode:2001PNAS...98.3034D. doi:10.1073/pnas.061487598. PMC 30602. PMID 11248027.
^ a bKristof 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". The Journal of Biological Chemistry. 278 (36): 33637–44. doi:10.1074/jbc.M301053200. PMID 12807916.
^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". Proceedings of the National Academy of Sciences of the United States of America. 97 (10): 5267–72. Bibcode:2000PNAS...97.5267L. doi:10.1073/pnas.97.10.5267. PMC 25817. PMID 10805787.
^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". The Journal of Biological Chemistry. 276 (22): 19512–23. doi:10.1074/jbc.M009063200. PMID 11278462.
^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". The EMBO Journal. 16 (6): 1291–304. doi:10.1093/emboj/16.6.1291. PMC 1169727. PMID 9135145.
^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". The Journal of Biological Chemistry. 276 (17): 13727–37. doi:10.1074/jbc.M011240200. PMID 11278865.
^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". The Journal of Biological Chemistry. 271 (10): 5790–4. doi:10.1074/jbc.271.10.5790. PMID 8621447.
^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". The Journal of Biological Chemistry. 274 (34): 24059–65. doi:10.1074/jbc.274.34.24059. PMID 10446176.
^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". The Journal of Biological Chemistry. 277 (33): 30072–8. doi:10.1074/jbc.M202943200. PMID 12048190.
^Gunaje JJ, Bhat GJ (October 2001). "Involvement of tyrosine phosphatase PTP1D in the inhibition of interleukin-6-induced Stat3 signaling by alpha-thrombin". Biochemical and Biophysical Research Communications. 288 (1): 252–7. doi:10.1006/bbrc.2001.5759. PMID 11594781.
^Spiekermann K, Biethahn S, Wilde S, Hiddemann W, Alves F (August 2001). "Constitutive activation of STAT transcription factors in acute myelogenous leukemia". European Journal of Haematology. 67 (2): 63–71. doi:10.1034/j.1600-0609.2001.t01-1-00385.x. PMID 11722592. S2CID 38074766.
^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". Biochemical and Biophysical Research Communications. 239 (2): 493–7. doi:10.1006/bbrc.1997.7493. PMID 9344858.
^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". Molecular and Cellular Biology. 20 (13): 4505–12. doi:10.1128/mcb.20.13.4505-4512.2000. PMC 85828. PMID 10848577.
Further reading[edit]
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. S2CID 22135982.
Kisseleva T, Bhattacharya S, Braunstein J, Schindler CW (February 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 (January 2005). "Nef: "necessary and enforcing factor" in HIV infection". Current HIV Research. 3 (1): 87–94. doi:10.2174/1570162052773013. PMID 15638726.
External links[edit]
FactorBook STAT1
vtePDB gallery
1bf5: TYROSINE PHOSPHORYLATED STAT-1/DNA COMPLEX
1yvl: Structure of Unphosphorylated STAT1
vteTranscription factors and intracellular receptors
(1) Basic domains
(1.1) Basic leucine zipper (bZIP)
Activating transcription factor
AATF
1
2
3
4
5
6
7
AP-1
c-Fos
FOSB
FOSL1
FOSL2
JDP2
c-Jun
JUNB
JunD
BACH
1
2
BATF
BLZF1
C/EBP
α
β
γ
δ
ε
ζ
CREB
1
3
L1
CREM
DBP
DDIT3
GABPA
GCN4
HLF
MAF
B
F
G
K
NFE
2
L1
L2
L3
NFIL3
NRL
NRF
1
2
3
XBP1
(1.2) Basic helix-loop-helix (bHLH)
Group A
AS-C
ASCL1
ASCL2
ATOH1
HAND
1
2
MESP2
Myogenic regulatory factors
MyoD
Myogenin
MYF5
MYF6
NeuroD
1
2
Neurogenins
1
2
3
OLIG
1
2
Paraxis
TCF15
Scleraxis
SLC
LYL1
TAL
1
2
Twist
Group B
FIGLA
Myc
c-Myc
l-Myc
n-Myc
MXD4
TCF4
Group CbHLH-PAS
AhR
AHRR
ARNT
ARNTL
ARNTL2
CLOCK
HIF
1A
EPAS1
3A
NPAS
1
2
3
SIM
1
2
Group D
BHLH
2
3
9
Pho4
ID
1
2
3
4
Group E
HES
1
2
3
4
5
6
7
HEY
1
2
L
Group FbHLH-COE
EBF1
(1.3) bHLH-ZIP
AP-4
MAX
MXD1
MXD3
MITF
MNT
MLX
MLXIPL
MXI1
Myc
SREBP
1
2
USF1
(1.4) NF-1
NFI
A
B
C
X
SMAD
R-SMAD
1
2
3
5
9
I-SMAD
6
7
4)
(1.5) RF-X
RFX
1
2
3
4
5
6
ANK
(1.6) Basic helix-span-helix (bHSH)
AP-2
α
β
γ
δ
ε
(2) Zinc finger DNA-binding domains
(2.1) Nuclear receptor (Cys4)
subfamily 1
Thyroid hormone
α
β
CAR
FXR
LXR
α
β
PPAR
α
β/δ
γ
PXR
RAR
α
β
γ
ROR
α
β
γ
Rev-ErbA
α
β
VDR
subfamily 2
COUP-TF
(I
II
Ear-2
HNF4
α
γ
PNR
RXR
α
β
γ
Testicular receptor
2
4
TLX
subfamily 3
Steroid hormone
Androgen
Estrogen
α
β
Glucocorticoid
Mineralocorticoid
Progesterone
Estrogen related
α
β
γ
subfamily 4
NUR
NGFIB
NOR1
NURR1
subfamily 5
LRH-1
SF1
subfamily 6
GCNF
subfamily 0
DAX1
SHP
(2.2) Other Cys4
GATA
1
2
3
4
5
6
MTA
1
2
3
TRPS1
(2.3) Cys2His2
General transcription factors
TFIIA
TFIIB
TFIID
TFIIE
1
2
TFIIF
1
2
TFIIH
1
2
4
2I
3A
3C1
3C2
ATBF1
BCL
6
11A
11B
CTCF
E4F1
EGR
1
2
3
4
ERV3
GFI1
GLI-Krüppel family
1
2
3
REST
S1
S2
YY1
HIC
1
2
HIVEP
1
2
3
IKZF
1
2
3
ILF
2
3
KLF
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
17
MTF1
MYT1
OSR1
PRDM9
SALL
1
2
3
4
SP
1
2
4
7
8
TSHZ3
WT1
Zbtb7
7A
7B
ZBTB
11
16
17
20
32
33
40
zinc finger
3
7
9
10
19
22
24
33B
34
35
41
43
44
51
74
143
146
148
165
202
217
219
238
239
259
267
268
281
295
300
318
330
346
350
365
366
384
423
451
452
471
593
638
644
649
655
804A
(2.4) Cys6
HIVEP1
(2.5) Alternating composition
AIRE
DIDO1
GRLF1
ING
1
2
4
JARID
1A
1B
1C
1D
2
JMJD1B
(2.6) WRKY
WRKY
(3) Helix-turn-helix domains
(3.1) Homeodomain
AntennapediaANTP class
protoHOXHox-like
ParaHox
Gsx
1
2
Xlox
PDX1
Cdx
1
2
4
extended Hox: Evx1
Evx2
MEOX1
MEOX2
Homeobox
A1
A2
A3
A4
A5
A7
A9
A10
A11
A13
B1
B2
B3
B4
B5
B6
B7
B8
B9
B13
C4
C5
C6
C8
C9
C10
C11
C12
C13
D1
D3
D4
D8
D9
D10
D11
D12
D13
GBX1
GBX2
MNX1
metaHOXNK-like
BARHL1
BARHL2
BARX1
BARX2
BSX
DBX
1
2
DLX
1
2
3
4
5
6
EMX
1
2
EN
1
2
HHEX
HLX
LBX1
LBX2
MSX
1
2
NANOG
NKX
2-1
2-2
2-3
2-5
3-1
3-2
HMX1
HMX2
HMX3
6-1
6-2
NATO
TLX1
TLX2
TLX3
VAX1
VAX2
other
ARX
CRX
CUTL1
FHL
1
2
3
HESX1
HOPX
LMX
1A
1B
NOBOX
TALE
IRX
1
2
3
4
5
6
MKX
MEIS
1
2
PBX
1
2
3
PKNOX
1
2
SIX
1
2
3
4
5
PHF
1
3
6
8
10
16
17
20
21A
POU domain
PIT-1
BRN-3: A
B
C
Octamer transcription factor: 1
2
3/4
6
7
11
SATB2
ZEB
1
2
(3.2) Paired box
PAX
1
2
3
4
5
6
7
8
9
PRRX
1
2
PROP1
PHOX
2A
2B
RAX
SHOX
SHOX2
VSX1
VSX2
Bicoid
GSC
BICD2
OTX
1
2
PITX
1
2
3
(3.3) Fork head / winged helix
E2F
1
2
3
4
5
FOX proteins
A1
A2
A3
C1
C2
D3
D4
E1
E3
F1
G1
H1
I1
J1
J2
K1
K2
L2
M1
N1
N3
O1
O3
O4
P1
P2
P3
P4
(3.4) Heat shock factors
HSF
1
2
4
(3.5) Tryptophan clusters
ELF
2
4
5
EGF
ELK
1
3
4
ERF
ETS
1
2
ERG
SPIB
ETV
1
4
5
6
FLI1
Interferon regulatory factors
1
2
3
4
5
6
7
8
MYB
MYBL2
(3.6) TEA domain
transcriptional enhancer factor
1
2
3
4
(4) β-Scaffold factors with minor groove contacts
(4.1) Rel homology region
NF-κB
NFKB1
NFKB2
REL
RELA
RELB
NFAT
C1
C2
C3
C4
5
(4.2) STAT
STAT
1
2
3
4
5
6
(4.3) p53-like
p53 p63 p73 family
p53
TP63
p73
TBX
1
2
3
5
19
21
22
TBR1
TBR2
TFT
MYRF
(4.4) MADS box
Mef2
A
B
C
D
SRF
(4.6) TATA-binding proteins
TBP
TBPL1
(4.7) High-mobility group
BBX
HMGB
1
2
3
4
HMGN
1
2
3
4
HNF
1A
1B
SOX
1
2
3
4
5
6
8
9
10
11
12
13
14
15
18
21
SRY
SSRP1
TCF/LEF
TCF
1
3
4
LEF1
TOX
1
2
3
4
(4.9) Grainyhead
TFCP2
(4.10) Cold-shock domain
CSDA
YBX1
(4.11) Runt
CBF
CBFA2T2
CBFA2T3
RUNX1
RUNX2
RUNX3
RUNX1T1
(0) Other transcription factors
(0.2) HMGI(Y)
HMGA
1
2
HBP1
(0.3) Pocket domain
Rb
RBL1
RBL2
(0.5) AP-2/EREBP-related factors
Apetala 2
EREBP
B3
(0.6) Miscellaneous
ARID
1A
1B
2
3A
3B
4A
CAP
IFI
16
35
MLL
2
3
T1
MNDA
NFY
A
B
C
Rho/Sigma
see also transcription factor/coregulator deficiencies