Abstract
Two members of the signal transducer and activator of transcription family, STAT1 and STAT2, form, together with interferon regulatory factor 9 (IRF-9), the ISGF3 complex that activates the expression of the interferon-stimulated genes (ISG). The ISGF3 complex also participates in the virus-induced alpha/beta interferon (IFN-alpha/beta) gene amplification cascade by up-regulating IRF-7 gene expression. Here, we show that treatment of cells with trichostatin A (TSA), a deacetylase inhibitor, inhibits the virus-induced activation of IFN-alpha/beta promoters and dramatically reduces the ability of different ISG promoters to respond to IFN stimulation. Impairment of IFN-alpha/beta and ISG expression by TSA in infected cells is due to the blockage of interferon-stimulated ISGF3 complex formation, which leads to the abolition of IRF-7 gene expression. We also show that the TSA-dependent inhibition of ISGF3 is related to impaired nuclear accumulation of STAT2. Our data suggest that an acetylation/deacetylation mechanism participates in the regulation of cellular distribution and function of STAT2 in IFN-alpha/beta signaling.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Line
-
Cell Nucleus / metabolism
-
Cytoplasm / metabolism
-
DNA-Binding Proteins / drug effects*
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism*
-
Down-Regulation*
-
Hydroxamic Acids / pharmacology*
-
Interferon Regulatory Factor-7
-
Interferon-Stimulated Gene Factor 3
-
Interferon-Stimulated Gene Factor 3, gamma Subunit
-
Interferon-alpha / pharmacology
-
Interferon-beta / pharmacology
-
Mice
-
Newcastle disease virus / immunology
-
Newcastle disease virus / pathogenicity
-
STAT1 Transcription Factor
-
STAT2 Transcription Factor
-
Trans-Activators / metabolism
-
Transcription Factors / drug effects*
-
Transcription Factors / genetics
-
Transcription Factors / metabolism*
Substances
-
DNA-Binding Proteins
-
Hydroxamic Acids
-
Interferon Regulatory Factor-7
-
Interferon-Stimulated Gene Factor 3
-
Interferon-Stimulated Gene Factor 3, gamma Subunit
-
Interferon-alpha
-
Irf7 protein, mouse
-
Isgf3g protein, mouse
-
STAT1 Transcription Factor
-
STAT2 Transcription Factor
-
Stat1 protein, mouse
-
Stat2 protein, mouse
-
Trans-Activators
-
Transcription Factors
-
trichostatin A
-
Interferon-beta