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== Function==
== Function==
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 (IFNa), Interferon gamma (IFNg), Epidermal Growth Factor (EGF), Platelet Derived Growth Factor (PDGF) or Interleukin 6 (IL-6)<ref name=":0">{{Cite journal|last=Baris|first=Safa|last2=Alroqi|first2=Fayhan|last3=Kiykim|first3=Ayca|last4=Karakoc-Aydiner|first4=Elif|last5=Ogulur|first5=Ismail|last6=Ozen|first6=Ahmet|last7=Charbonnier|first7=Louis-Marie|last8=Bakır|first8=Mustafa|last9=Boztug|first9=Kaan|date=2016-10-01|title=Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1|url=https://link.springer.com/article/10.1007/s10875-016-0312-3|journal=Journal of Clinical Immunology|language=en|volume=36|issue=7|pages=641–648|doi=10.1007/s10875-016-0312-3|issn=0271-9142}}</ref>

Type I interferons (IFN-a, IFN-b) 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 regulátory Factor 9. This allows STAT1 to enter the nucleus<ref>{{Cite web|url=http://www.genecards.org/cgi-bin/carddisp.pl?gene=IRF9|title=IRF9 Gene - GeneCards {{!}} IRF9 Protein {{!}} IRF9 Antibody|last=Database|first=GeneCards Human Gene|website=www.genecards.org|access-date=2017-06-01}}</ref>. STAT1 has a key role in many gene expressions that cause survival of the cell, viability or pathogen response. There are two possible trancripts (due to alternative splicing) that encode 2 isoforms of STAT1<ref>{{Cite web|url=http://www.uniprot.org/uniprot/P42224|title=STAT1 - Signal transducer and activator of transcription 1-alpha/beta - Homo sapiens (Human) - STAT1 gene & protein|website=www.uniprot.org|language=en|access-date=2017-06-01}}</ref> <ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/6772|title=STAT1 signal transducer and activator of transcription 1 [Homo sapiens (human)] - Gene - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2017-06-01}}</ref>

STAT1 is involved in upregulating genes due to a signal by either [[Interferon type I|type I]], [[Interferon type II|type II]], or [[Interferon type III|type III]] [[interferons]]. In response to [[Interferon-gamma|IFN-γ]] stimulation, STAT1 forms homodimers or heterodimers with [[STAT3]] that bind to the '''GAS''' (Interferon-'''G'''amma-'''A'''ctivated '''S'''equence) promoter element; in response to either [[Interferon type I|IFN-α or IFN-β]] stimulation, STAT1 forms a heterodimer with [[STAT2]] that can bind the '''ISRE''' ('''I'''nterferon-'''S'''timulated '''R'''esponse '''E'''lement) promoter element.<ref>{{cite journal | vauthors = Katze MG, He Y, Gale M | title = Viruses and interferon: a fight for supremacy | journal = Nature Reviews Immunology | volume = 2 | issue = 9 | pages = 675–87 | year = 2002 | pmid = 12209136 | doi = 10.1038/nri888 |display-authors = 2}}</ref> In either case, binding of the promoter element leads to an increased expression of '''ISG''' ('''I'''nterferon-'''S'''timulated '''G'''enes).
STAT1 is involved in upregulating genes due to a signal by either [[Interferon type I|type I]], [[Interferon type II|type II]], or [[Interferon type III|type III]] [[interferons]]. In response to [[Interferon-gamma|IFN-γ]] stimulation, STAT1 forms homodimers or heterodimers with [[STAT3]] that bind to the '''GAS''' (Interferon-'''G'''amma-'''A'''ctivated '''S'''equence) promoter element; in response to either [[Interferon type I|IFN-α or IFN-β]] stimulation, STAT1 forms a heterodimer with [[STAT2]] that can bind the '''ISRE''' ('''I'''nterferon-'''S'''timulated '''R'''esponse '''E'''lement) promoter element.<ref>{{cite journal | vauthors = Katze MG, He Y, Gale M | title = Viruses and interferon: a fight for supremacy | journal = Nature Reviews Immunology | volume = 2 | issue = 9 | pages = 675–87 | year = 2002 | pmid = 12209136 | doi = 10.1038/nri888 |display-authors = 2}}</ref> In either case, binding of the promoter element leads to an increased expression of '''ISG''' ('''I'''nterferon-'''S'''timulated '''G'''enes).


Expression of STAT1 can be induced with [[diallyl disulfide]], a compound in garlic.<ref>{{cite journal | vauthors = Lu HF, Yang JS, Lin YT, Tan TW, Ip SW, Li YC, Tsou MF, Chung JG | title = Diallyl disulfide induced signal transducer and activator of transcription 1 expression in human colon cancer colo 205 cells using differential display RT-PCR | journal = Cancer Genomics Proteomics. | volume = 4 | issue = 2 | pages = 93–7 | year = 2007 | pmid = 17804871 | doi = }}</ref>
Expression of STAT1 can be induced with [[diallyl disulfide]], a compound in garlic.<ref>{{cite journal | vauthors = Lu HF, Yang JS, Lin YT, Tan TW, Ip SW, Li YC, Tsou MF, Chung JG | title = Diallyl disulfide induced signal transducer and activator of transcription 1 expression in human colon cancer colo 205 cells using differential display RT-PCR | journal = Cancer Genomics Proteomics. | volume = 4 | issue = 2 | pages = 93–7 | year = 2007 | pmid = 17804871 | doi = }}</ref>

=== Mutations of STAT1 ===
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. Repeting common infections are frequent by both GOF and LOF mutations.

==== Loss of function ====
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 autosomal dominant mutation; phenotypically causes impaired IFNg responses and patients suffer with selective intracellular bacterial diseases (MSMD)<ref>{{Cite book|url=https://books.google.cz/books?id=VsiiDQAAQBAJ&pg=PA357&lpg=PA357&dq=STAT1+deficiency&source=bl&ots=TRFMoBNpCz&sig=_15MKohnxvkibnwenR2d-st1yEU&hl=cs&sa=X&ved=0ahUKEwiA_or7xOfSAhWFliwKHZIXAzE4ChDoAQhFMAU#v=onepage&q=STAT1&f=false|title=Primary Immunodeficiency Diseases: Definition, Diagnosis, and Management|last=Rezaei|first=Nima|last2=Aghamohammadi|first2=Asghar|last3=Notarangelo|first3=Luigi D.|date=2016-11-30|publisher=Springer|isbn=9783662529096|language=en}}</ref>

There were knock-out mice prepared in the 90s. There was discovered low amount of CD4<sup>+</sup> and CD25<sup>+</sup> regulatory T-cells and almost no IFNa, b and g response which lead to parasital, viral and bacterial infections. The very first reported case of STAT1 deficiency in human was autosomal dominant mutation and patients were showing propensity to mycobacterial infections. <sup>6</sup> Another case reported was about 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 not expected bacterial and viral infections, should be considered as potentially STAT1 deficient<ref>{{Cite journal|last=Chapgier|first=Ariane|last2=Kong|first2=Xiao-Fei|last3=Boisson-Dupuis|first3=Stéphanie|last4=Jouanguy|first4=Emmanuelle|last5=Averbuch|first5=Diana|last6=Feinberg|first6=Jacqueline|last7=Zhang|first7=Shen-Ying|last8=Bustamante|first8=Jacinta|last9=Vogt|first9=Guillaume|date=2009-06-01|title=A partial form of recessive STAT1 deficiency in humans|url=http://www.jci.org/articles/view/37083|journal=Journal of Clinical Investigation|language=en|volume=119|issue=6|pages=1502–1514|doi=10.1172/jci37083|issn=0021-9738}}</ref> <ref>{{Cite web|url=http://www.asid.ma/en/ressources/mini-reviews/171-defects-of-stat1-in-human-loss-of-function-exposes-to-mycobacteria-gain-of-function-exposes-to-candida.html|title=Defects of STAT1 in Human. Loss of Function exposes to Mycobacteria. Gain of Function exposes to Candida|last=|first=|date=|website=www.asid.ma|language=en-gb|archive-url=|archive-date=|dead-url=|access-date=2017-06-01}}</ref>

==== Gain of function ====
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 syndrom (hyper-IgE) and with autoimmune polyendocrine syndrom 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 patiens develop autimmunities 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 beeing tested and are a possible choice of treatment for these patients<ref>{{Cite journal|last=Toubiana|first=Julie|last2=Okada|first2=Satoshi|last3=Hiller|first3=Julia|last4=Oleastro|first4=Matias|last5=Gomez|first5=Macarena Lagos|last6=Becerra|first6=Juan Carlos Aldave|last7=Ouachée-Chardin|first7=Marie|last8=Fouyssac|first8=Fanny|last9=Girisha|first9=Katta Mohan|date=2016-06-23|title=Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype|url=http://www.bloodjournal.org/content/127/25/3154|journal=Blood|language=en|volume=127|issue=25|pages=3154–3164|doi=10.1182/blood-2015-11-679902|issn=0006-4971|pmc=PMC4920021|pmid=27114460}}</ref> <ref name=":0" /> <ref>{{Cite journal|last=Dupuis|first=Stéphanie|last2=Jouanguy|first2=Emmanuelle|last3=Al-Hajjar|first3=Sami|last4=Fieschi|first4=Claire|last5=Al-Mohsen|first5=Ibrahim Zaid|last6=Al-Jumaah|first6=Suliman|last7=Yang|first7=Kun|last8=Chapgier|first8=Ariane|last9=Eidenschenk|first9=Céline|date=March 2003|title=Impaired response to interferon-α/β and lethal viral disease in human STAT1 deficiency|url=http://www.nature.com/ng/journal/v33/n3/full/ng1097.html|journal=Nature Genetics|language=en|volume=33|issue=3|pages=388–391|doi=10.1038/ng1097|issn=1061-4036}}</ref>


== Interactions ==
== Interactions ==

Revision as of 14:47, 1 June 2017

STAT1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSTAT1, CANDF7, IMD31A, IMD31B, IMD31C, ISGF-3, STAT91, signal transducer and activator of transcription 1
External IDsOMIM: 600555 MGI: 103063 HomoloGene: 21428 GeneCards: STAT1
Orthologs
SpeciesHumanMouse
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 MbChr 1: 52.16 – 52.2 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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.

Function

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 (IFNa), Interferon gamma (IFNg), Epidermal Growth Factor (EGF), Platelet Derived Growth Factor (PDGF) or Interleukin 6 (IL-6)[5]

Type I interferons (IFN-a, IFN-b) 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 regulátory 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 trancripts (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

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. Repeting common infections are frequent by both GOF and LOF mutations.

Loss of function

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 autosomal dominant mutation; phenotypically causes impaired IFNg responses and patients suffer with selective intracellular bacterial diseases (MSMD)[11]

There were knock-out mice prepared in the 90s. There was discovered low amount of CD4+ and CD25+ regulatory T-cells and almost no IFNa, b and g response which lead to parasital, viral and bacterial infections. The very first reported case of STAT1 deficiency in human was autosomal dominant mutation and patients were showing propensity to mycobacterial infections. 6 Another case reported was about 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 not expected bacterial and viral infections, should be considered as potentially STAT1 deficient[12] [13]

Gain of function

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 syndrom (hyper-IgE) and with autoimmune polyendocrine syndrom 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 patiens develop autimmunities 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 beeing tested and are a possible choice of treatment for these patients[14] [5] [15]

Interactions

STAT1 has been shown to interact with:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000115415 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026104 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Baris, Safa; Alroqi, Fayhan; Kiykim, Ayca; Karakoc-Aydiner, Elif; Ogulur, Ismail; Ozen, Ahmet; Charbonnier, Louis-Marie; Bakır, Mustafa; Boztug, Kaan (2016-10-01). "Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1". Journal of Clinical Immunology. 36 (7): 641–648. doi:10.1007/s10875-016-0312-3. ISSN 0271-9142.
  6. ^ Database, GeneCards Human Gene. "IRF9 Gene - GeneCards | IRF9 Protein | IRF9 Antibody". www.genecards.org. Retrieved 2017-06-01.
  7. ^ "STAT1 - Signal transducer and activator of transcription 1-alpha/beta - Homo sapiens (Human) - STAT1 gene & protein". www.uniprot.org. Retrieved 2017-06-01.
  8. ^ "STAT1 signal transducer and activator of transcription 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-06-01.
  9. ^ 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.
  10. ^ 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.
  11. ^ Rezaei, Nima; Aghamohammadi, Asghar; Notarangelo, Luigi D. (2016-11-30). Primary Immunodeficiency Diseases: Definition, Diagnosis, and Management. Springer. ISBN 9783662529096.
  12. ^ Chapgier, Ariane; Kong, Xiao-Fei; Boisson-Dupuis, Stéphanie; Jouanguy, Emmanuelle; Averbuch, Diana; Feinberg, Jacqueline; Zhang, Shen-Ying; Bustamante, Jacinta; Vogt, Guillaume (2009-06-01). "A partial form of recessive STAT1 deficiency in humans". Journal of Clinical Investigation. 119 (6): 1502–1514. doi:10.1172/jci37083. ISSN 0021-9738.
  13. ^ "Defects of STAT1 in Human. Loss of Function exposes to Mycobacteria. Gain of Function exposes to Candida". www.asid.ma. Retrieved 2017-06-01. {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)
  14. ^ Toubiana, Julie; Okada, Satoshi; Hiller, Julia; Oleastro, Matias; Gomez, Macarena Lagos; Becerra, Juan Carlos Aldave; Ouachée-Chardin, Marie; Fouyssac, Fanny; Girisha, Katta Mohan (2016-06-23). "Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype". Blood. 127 (25): 3154–3164. doi:10.1182/blood-2015-11-679902. ISSN 0006-4971. PMC 4920021. PMID 27114460.{{cite journal}}: CS1 maint: PMC format (link)
  15. ^ Dupuis, Stéphanie; Jouanguy, Emmanuelle; Al-Hajjar, Sami; Fieschi, Claire; Al-Mohsen, Ibrahim Zaid; Al-Jumaah, Suliman; Yang, Kun; Chapgier, Ariane; Eidenschenk, Céline (March 2003). "Impaired response to interferon-α/β and lethal viral disease in human STAT1 deficiency". Nature Genetics. 33 (3): 388–391. doi:10.1038/ng1097. ISSN 1061-4036.
  16. ^ 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.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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.
  20. ^ 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.
  21. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  22. ^ a b 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  23. ^ 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.
  24. ^ 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.
  25. ^ 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.
  26. ^ a b 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  27. ^ 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.
  28. ^ 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. doi:10.1128/mcb.17.4.2048. PMC 232052. PMID 9121453.
  29. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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Further reading

External links

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