Signal transducer and activator of transcription 2 is a protein that in humans is encoded by the STAT2 gene.[1][2]
The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. In response to interferon (IFN), this protein forms a complex with STAT1 and IFN regulatory factor family protein p48 (ISGF3G), in which this protein acts as a transactivator, but lacks the ability to bind DNA directly. Transcription adaptor P300/CBP (EP300/CREBBP) has been shown to interact specifically with this protein, which is thought to be involved in the process of blocking IFN-alpha response by adenovirus.[2]
Interactions
STAT2 has been shown to interact with MED14,[3] CREB-binding protein,[4] SMARCA4,[5] STAT1,[6][7][8] IFNAR2,[9][10] IFNAR1[9][11][12] and ISGF3G.[13][14]
References
- ^ Yan R, Qureshi S, Zhong Z, Wen Z, Darnell JE Jr (Apr 1995). "The genomic structure of the STAT genes: multiple exons in coincident sites in Stat1 and Stat2". Nucleic Acids Res 23 (3): 459–63. doi:10.1093/nar/23.3.459. PMC 306697. PMID 7885841.
- ^ a b "Entrez Gene: STAT2 signal transducer and activator of transcription 2, 113kDa".
- ^ Lau, Joe F; Nusinzon Inna; Burakov Darya; Freedman Leonard P; Horvath Curt M (Jan 2003). "Role of metazoan mediator proteins in interferon-responsive transcription". Mol. Cell. Biol. (United States) 23 (2): 620–8. doi:10.1128/MCB.23.2.620-628.2003. ISSN 0270-7306. PMC 151539. PMID 12509459.
- ^ Bhattacharya, S; Eckner R; Grossman S; Oldread E; Arany Z; D'Andrea A; Livingston D M (Sep 1996). "Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha". Nature (ENGLAND) 383 (6598): 344–7. doi:10.1038/383344a0. ISSN 0028-0836. PMID 8848048.
- ^ Huang, Mei; Qian Feng; Hu Yuanyu; Ang Chengeng; Li Zhong; Wen Zilong (Oct 2002). "Chromatin-remodelling factor BRG1 selectively activates a subset of interferon-alpha-inducible genes". Nat. Cell Biol. (England) 4 (10): 774–81. doi:10.1038/ncb855. ISSN 1465-7392. PMID 12244326.
- ^ 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. doi:10.1074/jbc.271.10.5790. ISSN 0021-9258. PMID 8621447.
- ^ 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. doi:10.1074/jbc.274.34.24059. ISSN 0021-9258. PMID 10446176.
- ^ 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.
- ^ a b 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. PMC 232052. PMID 9121453.
- ^ Nguyen, Vinh-Phúc; Saleh Abu Z M; Arch Allison E; Yan Hai; Piazza Flavia; Kim John; Krolewski John J (Mar 2002). "Stat2 binding to the interferon-alpha receptor 2 subunit is not required for interferon-alpha signaling". J. Biol. Chem. (United States) 277 (12): 9713–21. doi:10.1074/jbc.M111161200. ISSN 0021-9258. PMID 11786546.
- ^ Uddin, S; Chamdin A; Platanias L C (Oct 1995). "Interaction of the transcriptional activator Stat-2 with the type I interferon receptor". J. Biol. Chem. (UNITED STATES) 270 (42): 24627–30. doi:10.1074/jbc.270.42.24627. ISSN 0021-9258. PMID 7559568.
- ^ Yan, H; Krishnan K; Greenlund A C; Gupta S; Lim J T; Schreiber R D; Schindler C W; Krolewski J J (Mar 1996). "Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 protein". EMBO J. (ENGLAND) 15 (5): 1064–74. ISSN 0261-4189. PMC 450004. PMID 8605876.
- ^ 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. PMC 231699. PMID 8943351.
- ^ Martinez-Moczygemba, M; Gutch M J; French D L; Reich N C (Aug 1997). "Distinct STAT structure promotes interaction of STAT2 with the p48 subunit of the interferon-alpha-stimulated transcription factor ISGF3". J. Biol. Chem. (UNITED STATES) 272 (32): 20070–6. doi:10.1074/jbc.272.32.20070. ISSN 0021-9258. PMID 9242679.
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.
- Fu XY, Schindler C, Improta T et al. (1992). "The proteins of ISGF-3, the interferon alpha-induced transcriptional activator, define a gene family involved in signal transduction". Proc. Natl. Acad. Sci. U.S.A. 89 (16): 7840–3. doi:10.1073/pnas.89.16.7840. PMC 49807. PMID 1502204.
- Uddin S, Chamdin A, Platanias LC (1995). "Interaction of the transcriptional activator Stat-2 with the type I interferon receptor". J. Biol. Chem. 270 (42): 24627–30. doi:10.1074/jbc.270.42.24627. PMID 7559568.
- Marrero MB, Schieffer B, Paxton WG et al. (1995). "Direct stimulation of Jak/STAT pathway by the angiotensin II AT1 receptor". Nature 375 (6528): 247–50. doi:10.1038/375247a0. PMID 7746328.
- Sugiyama T, Nishio Y, Kishimoto T, Akira S (1996). "Identification of alternative splicing form of Stat2". FEBS Lett. 381 (3): 191–4. doi:10.1016/0014-5793(96)00121-4. PMID 8601453.
- Yan H, Krishnan K, Greenlund AC et al. (1996). "Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 protein". EMBO J. 15 (5): 1064–74. PMC 450004. PMID 8605876.
- Gupta S, Yan H, Wong LH et al. (1996). "The SH2 domains of Stat1 and Stat2 mediate multiple interactions in the transduction of IFN-alpha signals". EMBO J. 15 (5): 1075–84. PMC 450005. PMID 8605877.
- Li X, Leung S, Qureshi S et al. (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.
- Bhattacharya S, Eckner R, Grossman S et al. (1996). "Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha". Nature 383 (6598): 344–7. doi:10.1038/383344a0. PMID 8848048.
- Horvath CM, Stark GR, Kerr IM, Darnell JE (1997). "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.
- Bluyssen HA, Levy DE (1997). "Stat2 is a transcriptional activator that requires sequence-specific contacts provided by stat1 and p48 for stable interaction with DNA". J. Biol. Chem. 272 (7): 4600–5. doi:10.1074/jbc.272.7.4600. PMID 9020188.
- Li X, Leung S, Kerr IM, Stark GR (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.
- Martinez-Moczygemba M, Gutch MJ, French DL, Reich NC (1997). "Distinct STAT structure promotes interaction of STAT2 with the p48 subunit of the interferon-alpha-stimulated transcription factor ISGF3". J. Biol. Chem. 272 (32): 20070–6. doi:10.1074/jbc.272.32.20070. PMID 9242679.
- Mowen K, David M (1998). "Role of the STAT1-SH2 domain and STAT2 in the activation and nuclear translocation of STAT1". J. Biol. Chem. 273 (46): 30073–6. doi:10.1074/jbc.273.46.30073. PMID 9804758.
- Dumler I, Kopmann A, Wagner K et al. (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.
- Paulson M, Pisharody S, Pan L et al. (1999). "Stat protein transactivation domains recruit p300/CBP through widely divergent sequences". J. Biol. Chem. 274 (36): 25343–9. doi:10.1074/jbc.274.36.25343. PMID 10464260.
- Gupta S, Jiang M, Pernis AB (1999). "IFN-alpha activates Stat6 and leads to the formation of Stat2:Stat6 complexes in B cells". J. Immunol. 163 (7): 3834–41. PMID 10490982.
- Vila-Coro AJ, Rodríguez-Frade JM, Martín De Ana A et al. (1999). "The chemokine SDF-1alpha triggers CXCR4 receptor dimerization and activates the JAK/STAT pathway". FASEB J. 13 (13): 1699–710. PMID 10506573.
External links
- STAT2 Transcription Factor at the US National Library of Medicine Medical Subject Headings (MeSH)
- FactorBook STAT2
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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