STAT3

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Signal transducer and activator of transcription 3 (acute-phase response factor)
信号转导及转录激活蛋白3(急性期反应因子)

PDB rendering based on 1bg1.
有效结构
PDB 直系同源检索:PDBe, RCSB
标识
代号 STAT3; APRF; HIES
扩展标识 遗传学102582 鼠基因103038 同源基因7960 ChEMBL: 4026 GeneCards: STAT3 Gene
RNA表达模式
PBB GE STAT3 208991 at tn.png
PBB GE STAT3 208992 s at tn.png
PBB GE STAT3 gnf1h01250 at tn.png
更多表达数据
直系同源体
物种 人类 鼠类
Entrez 6774 20848
Ensembl ENSG00000168610 ENSMUSG00000004040
UniProt P40763 P42227
mRNA序列 NM_003150 NM_011486
蛋白序列 NP_003141 NP_035616
基因位置 Chr 17:
40.47 – 40.54 Mb
Chr 11:
100.89 – 100.94 Mb
PubMed查询 [1] [2]

信号转导及转录激活蛋白3英语Signal transducer and activator of transcription 3STAT3)是一种由人类基因STAT3 编码的转录因子[1]

功能[编辑]

临床意义[编辑]

在癌症中的双重作用[编辑]

相互作用[编辑]

STAT3能与下列蛋白質发生交互作用

参考文献[编辑]

  1. ^ Akira S, Nishio Y, Inoue M, Wang XJ, Wei S, Matsusaka T, Yoshida K, Sudo T, Naruto M, Kishimoto T. Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway. Cell. April 1994, 77 (1): 63–71. doi:10.1016/0092-8674(94)90235-6. PMID 7512451. 
  2. ^ 2.0 2.1 Ueda T, Bruchovsky N, Sadar MD. Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways. J. Biol. Chem. 2002, 277 (9): 7076–85. doi:10.1074/jbc.M108255200. PMID 11751884. 
  3. ^ Matsuda T, Junicho A, Yamamoto T, Kishi H, Korkmaz K, Saatcioglu F, Fuse H, Muraguchi A. Cross-talk between signal transducer and activator of transcription 3 and androgen receptor signaling in prostate carcinoma cells. Biochem. Biophys. Res. Commun. 2001, 283 (1): 179–87. doi:10.1006/bbrc.2001.4758. PMID 11322786. 
  4. ^ Collum RG, Brutsaert S, Lee G, Schindler C. A Stat3-interacting protein (StIP1) regulates cytokine signal transduction. Proc. Natl. Acad. Sci. U.S.A. 2000, 97 (18): 10120–5. doi:10.1073/pnas.170192197. PMC 27739. PMID 10954736. 
  5. ^ Nakashima K, Yanagisawa M, Arakawa H, Kimura N, Hisatsune T, Kawabata M, Miyazono K, Taga T. Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300. Science. 1999, 284 (5413): 479–82. doi:10.1126/science.284.5413.479. PMID 10205054. 
  6. ^ 6.0 6.1 Yuan ZL, Guan YJ, Wang L, Wei W, Kane AB, Chin YE. Central role of the threonine residue within the p+1 loop of receptor tyrosine kinase in STAT3 constitutive phosphorylation in metastatic cancer cells. Mol. Cell. Biol. 2004, 24 (21): 9390–400. doi:10.1128/MCB.24.21.9390-9400.2004. PMC 522220. PMID 15485908. 
  7. ^ Olayioye MA, Beuvink I, Horsch K, Daly JM, Hynes NE. ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases. J. Biol. Chem. 1999, 274 (24): 17209–18. doi:10.1074/jbc.274.24.17209. PMID 10358079. 
  8. ^ Jung JE, Kim HS, Lee CS, Shin YJ, Kim YN, Kang GH, Kim TY, Juhnn YS, Kim SJ, Park JW, Ye SK, Chung MH. STAT3 inhibits the degradation of HIF-1alpha by pVHL-mediated ubiquitination. Exp. Mol. Med. 2008, 40 (5): 479–85. doi:10.3858/emm.2008.40.5.479. PMC 2679355. PMID 18985005. 
  9. ^ 9.0 9.1 Spiekermann K, Biethahn S, Wilde S, Hiddemann W, Alves F. Constitutive activation of STAT transcription factors in acute myelogenous leukemia. Eur. J. Haematol. 2001, 67 (2): 63–71. PMID 11722592. 
  10. ^ Zhang X, Wrzeszczynska MH, Horvath CM, Darnell JE. Interacting regions in Stat3 and c-Jun that participate in cooperative transcriptional activation. Mol. Cell. Biol. 1999, 19 (10): 7138–46. PMC 84707. PMID 10490649. 
  11. ^ Sanchez-Margalet V, Martin-Romero C. Human leptin signaling in human peripheral blood mononuclear cells: activation of the JAK-STAT pathway. Cell. Immunol. 2001, 211 (1): 30–6. doi:10.1006/cimm.2001.1815. PMID 11585385. 
  12. ^ Yokogami K, Wakisaka S, Avruch J, Reeves SA. Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR. Curr. Biol. 2000, 10 (1): 47–50. doi:10.1016/S0960-9822(99)00268-7. PMID 10660304. 
  13. ^ Kusaba H, Ghosh P, Derin R, Buchholz M, Sasaki C, Madara K, Longo DL. Interleukin-12-induced interferon-gamma production by human peripheral blood T cells is regulated by mammalian target of rapamycin (mTOR). J. Biol. Chem. 2005, 280 (2): 1037–43. doi:10.1074/jbc.M405204200. PMID 15522880. 
  14. ^ Kataoka Y, Matsumura I, Ezoe S, Nakata S, Takigawa E, Sato Y, Kawasaki A, Yokota T, Nakajima K, Felsani A, Kanakura Y. Reciprocal inhibition between MyoD and STAT3 in the regulation of growth and differentiation of myoblasts. J. Biol. Chem. 2003, 278 (45): 44178–87. doi:10.1074/jbc.M304884200. PMID 12947115. 
  15. ^ Zhang J, Yang J, Roy SK, Tininini S, Hu J, Bromberg JF, Poli V, Stark GR, Kalvakolanu DV. The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3. Proc. Natl. Acad. Sci. U.S.A. 2003, 100 (16): 9342–7. doi:10.1073/pnas.1633516100. PMC 170920. PMID 12867595. 
  16. ^ 16.0 16.1 Yu Z, Zhang W, Kone BC. Signal transducers and activators of transcription 3 (STAT3) inhibits transcription of the inducible nitric oxide synthase gene by interacting with nuclear factor kappaB. Biochem. J. 2002, 367 (Pt 1): 97–105. doi:10.1042/BJ20020588. PMC 1222853. PMID 12057007. 
  17. ^ Lerner L, Henriksen MA, Zhang X, Darnell JE. STAT3-dependent enhanceosome assembly and disassembly: synergy with GR for full transcriptional increase of the alpha 2-macroglobulin gene. Genes Dev. 2003, 17 (20): 2564–77. doi:10.1101/gad.1135003. PMC 218150. PMID 14522952. 
  18. ^ Zhang Z, Jones S, Hagood JS, Fuentes NL, Fuller GM. STAT3 acts as a co-activator of glucocorticoid receptor signaling. J. Biol. Chem. 1997, 272 (49): 30607–10. doi:10.1074/jbc.272.49.30607. PMID 9388192. 
  19. ^ Giraud S, Bienvenu F, Avril S, Gascan H, Heery DM, Coqueret O. Functional interaction of STAT3 transcription factor with the coactivator NcoA/SRC1a. J. Biol. Chem. 2002, 277 (10): 8004–11. doi:10.1074/jbc.M111486200. PMID 11773079. 
  20. ^ Kawasaki A, Matsumura I, Kataoka Y, Takigawa E, Nakajima K, Kanakura Y. Opposing effects of PML and PML/RAR alpha on STAT3 activity. Blood. 2003, 101 (9): 3668–73. doi:10.1182/blood-2002-08-2474. PMID 12506013. 
  21. ^ Simon AR, Vikis HG, Stewart S, Fanburg BL, Cochran BH, Guan KL. Regulation of STAT3 by direct binding to the Rac1 GTPase. Science. 2000, 290 (5489): 144–7. doi:10.1126/science.290.5489.144. PMID 11021801. 
  22. ^ Hwang JH, Kim DW, Suh JM, Kim H, Song JH, Hwang ES, Park KC, Chung HK, Kim JM, Lee TH, Yu DY, Shong M. Activation of signal transducer and activator of transcription 3 by oncogenic RET/PTC (rearranged in transformation/papillary thyroid carcinoma) tyrosine kinase: roles in specific gene regulation and cellular transformation. Mol. Endocrinol. 2003, 17 (6): 1155–66. doi:10.1210/me.2002-0401. PMID 12637586. 
  23. ^ Schuringa JJ, Wojtachnio K, Hagens W, Vellenga E, Buys CH, Hofstra R, Kruijer W. MEN2A-RET-induced cellular transformation by activation of STAT3. Oncogene. 2001, 20 (38): 5350–8. doi:10.1038/sj.onc.1204715. PMID 11536047. 
  24. ^ Kim J, Kim D, Chung J. Replication protein a 32 kDa subunit (RPA p32) binds the SH2 domain of STAT3 and regulates its transcriptional activity. Cell Biol. Int. 2000, 24 (7): 467–73. doi:10.1006/cbir.2000.0525. PMID 10875894. 
  25. ^ Gunaje JJ, Bhat GJ. Involvement of tyrosine phosphatase PTP1D in the inhibition of interleukin-6-induced Stat3 signaling by alpha-thrombin. Biochem. Biophys. Res. Commun. 2001, 288 (1): 252–7. doi:10.1006/bbrc.2001.5759. PMID 11594781. 
  26. ^ Xia L, Wang L, Chung AS, Ivanov SS, Ling MY, Dragoi AM, Platt A, Gilmer TM, Fu XY, Chin YE. 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. 2002, 277 (34): 30716–23. doi:10.1074/jbc.M202823200. PMID 12070153. 
  27. ^ Cao X, Tay A, Guy GR, Tan YH. Activation and association of Stat3 with Src in v-Src-transformed cell lines. Mol. Cell. Biol. 1996, 16 (4): 1595–603. PMC 231145. PMID 8657134. 
  28. ^ Chung YH, Cho NH, Garcia MI, Lee SH, Feng P, Jung JU. Activation of Stat3 transcription factor by Herpesvirus saimiri STP-A oncoprotein. J. Virol. 2004, 78 (12): 6489–97. doi:10.1128/JVI.78.12.6489-6497.2004. PMC 416526. PMID 15163742. 

延伸阅读[编辑]

  • Hoey T, Grusby MJ. STATs as mediators of cytokine-induced responses. Adv. Immunol. Advances in Immunology. 1999, 71: 145–162. doi:10.1016/S0065-2776(08)60401-0. ISBN 978-0-12-022471-5. PMID 9917912. 
  • Kisseleva T, Bhattacharya S, Braunstein J, Schindler CW. Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene. 2002, 285 (1–2): 1–24. doi:10.1016/S0378-1119(02)00398-0. PMID 12039028. 
  • Joseph AM, Kumar M, Mitra D. Nef: "necessary and enforcing factor" in HIV infection. Curr. HIV Res. 2005, 3 (1): 87–94. doi:10.2174/1570162052773013. PMID 15638726. 
  • Inghirami G, Chiarle R, Simmons WJ et al. New and old functions of STAT3: a pivotal target for individualized treatment of cancer. Cell Cycle. 2006, 4 (9): 1131–3. PMID 16082218. 
  • Leeman RJ, Lui VW, Grandis JR. STAT3 as a therapeutic target in head and neck cancer. Expert opinion on biological therapy. 2006, 6 (3): 231–241. doi:10.1517/14712598.6.3.231. PMID 16503733. 
  • Aggarwal BB, Sethi G, Ahn KS et al. Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: modern target but ancient solution. Ann. N. Y. Acad. Sci. 2007, 1091: 151–169. doi:10.1196/annals.1378.063. PMID 17341611. 

外部链接[编辑]