Nuclear beta-arrestin1 functions as a scaffold for the dephosphorylation of STAT1 and moderates the antiviral activity of IFN-gamma Journal Article


Authors: Mo, W.; Zhang, L.; Yang, G. H.; Zhai, J. W.; Hu, Z. H.; Chen, Y. L.; Chen, X.; Hui, L.; Huang, R. M.; Hu, G. X.
Article Title: Nuclear beta-arrestin1 functions as a scaffold for the dephosphorylation of STAT1 and moderates the antiviral activity of IFN-gamma
Abstract: Signal transducers and activators of transcription 1 (STAT1) is activated by tyrosine phosphorylation upon interferon-gamma (IFN-gamma) stimulation. Phosphorylated STAT1 translocates into nucleus to initiate the transcription of IFN-gamma target genes that are important in mediating antiviral, anti proliferative, and immune response. The inactivation of STAT1 is mainly accomplished via tyrosine dephosphorylation by the nuclear isoform of T cell protein tyrosine phosphatase (TC45) in nucleus. Here we show that beta-arrestin1 directly interacts with STAT1 in nucleus after IFN-gamma treatment and accelerates STAT1 tyrosine dephosphorylation by recruiting TC45. Consequently, beta-arrestin1 negatively regulates STAT1 transcription activity as well as the IFN-gamma-induced gene transcription. Application of beta-arrestin1 siRNA significantly enhances IFN-gamma-induced antiviral response in vesicular stomatitis virus (VSV)-infected cells. Our results reveal that nuclear beta-arrestin1, acting as a scaffold for the dephosphorylation of STAT1, is an essential negative regulator of IFN-gamma signaling and participates in the IFN-y-induced cellular antiviral response.
Keywords: transcription factor; phosphorylation; gene activation; receptor; interferon-gamma; virus; protein-tyrosine-phosphatase; beta-arrestins; requires; jak
Journal Title: Molecular Cell
Volume: 31
Issue: 5
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2008-09-05
Start Page: 695
End Page: 707
Language: English
ACCESSION: WOS:000259113800011
DOI: 10.1016/j.molcel.2008.06.017
PROVIDER: wos
PUBMED: 18775329
Notes: --- - Article - "Source: Wos"
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  1. Ruimin Huang
    30 Huang