Signal transducer and activator of transcription 2

Definition:

Signal transducer and activator of transcription that mediates signaling by type I interferons (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize, associate with IRF9/ISGF3G 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 interferon stimulated genes, which drive the cell in an antiviral state. In addition, has also a negative feedback regulatory role in the type I interferon signaling by recruiting USP18 to the type I IFN receptor subunit IFNAR2 thereby mitigating the response to type I IFNs. Acts as a regulator of mitochondrial fission by modulating the phosphorylation of DNM1L at 'Ser-616' and 'Ser-637' which activate and inactivate the GTPase activity of DNM1L respectively.

References:

[1]. Sophie Hambleton, et al. STAT2 deficiency and susceptibility to viral illness in humans. Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):3053-8. [Content Brief]

[2]. Kei-Ichiro Arimoto, et al. STAT2 is an essential adaptor in USP18-mediated suppression of type I interferon signaling. Nat Struct Mol Biol. 2017 Mar;24(3):279-289. [Content Brief]

[3]. Rojeen Shahni, et al. Signal transducer and activator of transcription 2 deficiency is a novel disorder of mitochondrial fission. Brain. 2015 Oct;138(Pt 10):2834-46. [Content Brief]

[4]. Conor Gruber, et al. Homozygous STAT2 gain-of-function mutation by loss of USP18 activity in a patient with type I interferonopathy. J Exp Med. 2020 May 4;217(5):e20192319. [Content Brief]

[5]. Christopher J A Duncan, et al. Severe type I interferonopathy and unrestrained interferon signaling due to a homozygous germline mutation in STAT2. Sci Immunol. 2019 Dec 13;4(42):eaav7501. [Content Brief]

[6]. H A Bluyssen, et al. Stat2 is a transcriptional activator that requires sequence-specific contacts provided by stat1 and p48 for stable interaction with DNA. J Biol Chem. 1997 Feb 14;272(7):4600-5. [Content Brief]

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