Signal transducer and activator of transcription 3

Definition:

Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA. Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): deacetylation and oxidation of lysine residues by LOXL3, leads to disrupt STAT3 dimerization and inhibit its transcription activity. Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1. Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation (By similarity). May play an apoptotic role by transctivating BIRC5 expression under LEP activation. Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity. Plays a crucial role in basal beta cell functions, such as regulation of insulin secretion (By similarity).

References:

[1]. Shensi Shen, et al. Cytoplasmic STAT3 represses autophagy by inhibiting PKR activity. Mol Cell. 2012 Dec 14;48(5):667-80. [Content Brief]

[2]. Xueliang Gao, et al. Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase. Mol Cell. 2012 Mar 9;45(5):598-609. [Content Brief]

[3]. Haiping Jiang, et al. Upregulation of survivin by leptin/STAT3 signaling in MCF-7 cells. Biochem Biophys Res Commun. 2008 Mar 28;368(1):1-5. [Content Brief]

[4]. Alexandra Dreuw, et al. Characterization of the signaling capacities of the novel gp130-like cytokine receptor. J Biol Chem. 2004 Aug 20;279(34):36112-20. [Content Brief]

[5]. Y T Tsai, et al. Etk, a Btk family tyrosine kinase, mediates cellular transformation by linking Src to STAT3 activation. Mol Cell Biol. 2000 Mar;20(6):2043-54. [Content Brief]

[6]. Li Ma, et al. Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 Deacetylation and Deacetylimination Modulation. Mol Cell. 2017 Jan 19;65(2):296-309. [Content Brief]

[7]. Huang Shao, et al. Identification and characterization of signal transducer and activator of transcription 3 recruitment sites within the epidermal growth factor receptor. Cancer Res. 2003 Jul 15;63(14):3923-30. [Content Brief]

[8]. Tetsuya Yamamoto, et al. The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation. Biochem Biophys Res Commun. 2002 Oct 4;297(4):811-7. [Content Brief]

[9]. Neeraj K Saxena, et al. leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3. J Biol Chem. 2007 May 4;282(18):13316-25. [Content Brief]

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