Signal transducer and activator of transcription 1-alpha/beta

Definition

Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors. Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of IFN-stimulated genes (ISG), which drive the cell in an antiviral state. In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated. It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state. Becomes activated in response to KITLG/SCF and KIT signaling. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4.

References:

[1]. Daniela Ungureanu, et al. PIAS proteins promote SUMO-1 conjugation to STAT1. Blood. 2003 Nov 1;102(9):3311-3. [Content Brief]

[2]. B Liu, et al. Inhibition of Stat1-mediated gene activation by PIAS1. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10626-31. [Content Brief]

[3]. Tracie A DeVries, et al. Protein kinase Cdelta regulates apoptosis via activation of STAT1. J Biol Chem. 2004 Oct 29;279(44):45603-12. [Content Brief]

[4]. Richard S Rogers, et al. SUMO modification of STAT1 and its role in PIAS-mediated inhibition of gene activation. J Biol Chem. 2003 Aug 8;278(32):30091-7. [Content Brief]

[5]. Kun Chen, et al. Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity. Cell. 2017 Jul 27;170(3):492-506.e14. [Content Brief]

[6]. Noémie Alphonse, et al. A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling. Cell. 2022 Jun 23;185(13):2354-2369.e17. [Content Brief]

[7]. A C Greenlund, et al. Ligand-induced IFN gamma receptor tyrosine phosphorylation couples the receptor to its signal transduction system (p91). EMBO J. 1994 Apr 1;13(7):1591-600. [Content Brief]

[8]. Meng Li, et al. Interleukin-35 inhibits lipopolysaccharide-induced endothelial cell activation by downregulating inflammation and apoptosis. Exp Cell Res. 2021 Oct 15;407(2):112784. [Content Brief]

[9]. Yong Zhang, et al. PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection. Nat Immunol. 2015 Dec;16(12):1215-27. [Content Brief]

[10]. Pavel Krejci, et al. Analysis of STAT1 activation by six FGFR3 mutants associated with skeletal dysplasia undermines dominant role of STAT1 in FGFR3 signaling in cartilage. PLoS One. 2008;3(12):e3961. [Content Brief]

生物医学辞典

生物医学辞典は、生物学の学術用語と専門データの包括的で専門的なデータベースです。すべての説明は、権威ある書籍や高いＩＦの文献に基づいており、知りたい生物医学用語の正確な説明を得ることができます。

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