STAT3

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Signal transducer and activator of transcription 3 (acute-phase response factor)
信號轉導及轉錄激活蛋白3（急性期反應因子）
PDB rendering based on 1bg1.
有效結構
PDB 直系同源檢索：PDBe, RCSB
標識
代號 STAT3; APRF; HIES
擴展標識 遺傳學：102582 鼠基因：103038 同源基因：7960 ChEMBL: 4026 GeneCards: STAT3 Gene
RNA表達模式
更多表達數據
直系同源體
物種 人類 小鼠
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查詢 [1] [2]

信號轉導及轉錄激活蛋白3（英語：Signal transducer and activator of transcription 3，STAT3）是一種由人類基因STAT3 編碼的轉錄因子[1]。

功能[編輯]

STAT3是STAT蛋白家族的成員。受到細胞因子和生長因子的調節，STAT3被受體相關的Janus激酶（JAK）磷酸化，形成同源或異源二聚體，並轉移到細胞核，在那裡它們起轉錄激活劑的作用。具體而言，干擾素，表皮生長因子（EGF），白血球介素（IL-5和IL-6）等配體作用於受體，導致酪氨酸705磷酸化後，STAT3被激活。此外，STAT3可能通過絲裂原活化蛋白激酶（MAPK）[2]和c-src非受體酪氨酸激酶磷酸化絲氨酸727而激活。[3][4]STAT3介導響應細胞刺激的各種基因的表達，因此在許多細胞過程如細胞生長和細胞凋亡中起關鍵作用。[5]

當原腸胚形成開始時，STAT3缺陷的小鼠胚胎不能在胚胎發育第7天以後發育。[6]看來在這些發育的早期階段，STAT3激活是胚胎幹細胞（ESC）自我更新所必需的。事實上，如果STAT3通過其他方式被激活，LIF可以被省略，該LIF被提供給小鼠ESC培養物以保持其未分化狀態。[7]

STAT3對於TH17輔助性T細胞的分化至關重要，TH17輔助性T細胞已涉及多種自體免疫性疾病。[8]在病毒感染期間，缺乏T細胞中STAT3的小鼠顯示產生T-濾泡輔助（Tfh）細胞的能力受損，並且不能維持基於抗體的免疫性。[9]

臨床意義[編輯]

在癌症中的雙重作用[編輯]

相互作用[編輯]

STAT3能與下列蛋白質發生交互作用：

參考文獻[編輯]

  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. PMID 7512451. doi:10.1016/0092-8674(94)90235-6. 
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  4. ^ Lim, Cheh Peng; Cao, Xinmin. Structure, function, and regulation of STAT proteins. Molecular bioSystems. November 2006, 2 (11): 536–550 [2018-02-11]. ISSN 1742-206X. PMID 17216035. doi:10.1039/b606246f. （原始內容存檔於2018-02-18）. 
  5. ^ Yuan, Zheng-Long; Guan, Ying-Jie; Wang, Lijuan; Wei, Wenyi; Kane, Agnes B.; Chin, Y. Eugene. Central role of the threonine residue within the p+1 loop of receptor tyrosine kinase in STAT3 constitutive phosphorylation in metastatic cancer cells. Molecular and Cellular Biology. November 2004, 24 (21): 9390–9400 [2018-02-11]. ISSN 0270-7306. PMID 15485908. doi:10.1128/MCB.24.21.9390-9400.2004. （原始內容存檔於2018-02-18）. 
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  12. ^ 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. PMC 27739 可免費查閱. PMID 10954736. doi:10.1073/pnas.170192197. 
  13. ^ 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. PMID 10205054. doi:10.1126/science.284.5413.479. 
  14. ^ 14.0 14.1 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. PMC 522220 可免費查閱. PMID 15485908. doi:10.1128/MCB.24.21.9390-9400.2004. 
  15. ^ 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. PMID 10358079. doi:10.1074/jbc.274.24.17209. 
  16. ^ 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. PMC 2679355 可免費查閱. PMID 18985005. doi:10.3858/emm.2008.40.5.479. 
  17. ^ 17.0 17.1 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. 
  18. ^ 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 可免費查閱. PMID 10490649. 
  19. ^ 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. PMID 11585385. doi:10.1006/cimm.2001.1815. 
  20. ^ 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. PMID 10660304. doi:10.1016/S0960-9822(99)00268-7. 
  21. ^ 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. PMID 15522880. doi:10.1074/jbc.M405204200. 
  22. ^ 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. PMID 12947115. doi:10.1074/jbc.M304884200. 
  23. ^ 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. PMC 170920 可免費查閱. PMID 12867595. doi:10.1073/pnas.1633516100. 
  24. ^ 24.0 24.1 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. PMC 1222853 可免費查閱. PMID 12057007. doi:10.1042/BJ20020588. 
  25. ^ 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. PMC 218150 可免費查閱. PMID 14522952. doi:10.1101/gad.1135003. 
  26. ^ 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. PMID 9388192. doi:10.1074/jbc.272.49.30607. 
  27. ^ 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. PMID 11773079. doi:10.1074/jbc.M111486200. 
  28. ^ 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. PMID 12506013. doi:10.1182/blood-2002-08-2474. 
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  30. ^ 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. PMID 12637586. doi:10.1210/me.2002-0401. 
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  32. ^ 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. PMID 10875894. doi:10.1006/cbir.2000.0525. 
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  34. ^ 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. PMID 12070153. doi:10.1074/jbc.M202823200. 
  35. ^ 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 可免費查閱. PMID 8657134. 
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延伸閱讀[編輯]

  • Hoey T, Grusby MJ. STATs as mediators of cytokine-induced responses. Adv. Immunol. Advances in Immunology. 1999, 71: 145–162. ISBN 978-0-12-022471-5. PMID 9917912. doi:10.1016/S0065-2776(08)60401-0. 
  • 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. PMID 12039028. doi:10.1016/S0378-1119(02)00398-0. 
  • Joseph AM, Kumar M, Mitra D. Nef: "necessary and enforcing factor" in HIV infection. Curr. HIV Res. 2005, 3 (1): 87–94. PMID 15638726. doi:10.2174/1570162052773013. 
  • 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.  已忽略未知參數|author-separator= (幫助)
  • 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. PMID 16503733. doi:10.1517/14712598.6.3.231. 
  • 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. PMID 17341611. doi:10.1196/annals.1378.063.  已忽略未知參數|author-separator= (幫助)

外部連結[編輯]

配體
細胞因子受體
JAK激酶
銜接體蛋白
 
描述
取自「https://zh.wikipedia.org/w/index.php?title=STAT3&oldid=69717647」