Akt1 phosphorylates the transcriptional repressor EMSY, relieving its repression of interferon-stimulated genes and inhibiting the replication of HSV-1 and vesicular stomatitis virus.
Akt1 regulates antiviral immunity by phosphorylating EMSY, thereby relieving its repression of interferon-stimulated genes.
The protein kinases Akt1, Akt2, and Akt3 possess nonredundant signaling properties, few of which have been investigated. Here, we present evidence for an Akt1-dependent pathway that controls interferon (IFN)-regulated gene expression and antiviral immunity. The target of this pathway is EMSY, an oncogenic interacting partner of BRCA2 that functions as a transcriptional repressor. Overexpression of EMSY in hTERT-immortalized mammary epithelial cells, and in breast and ovarian carcinoma cell lines, represses IFN-stimulated genes (ISGs) in a BRCA2-dependent manner, whereas its knockdown has the opposite effect. EMSY binds to the promoters of ISGs, suggesting that EMSY functions as a direct transcriptional repressor. Akt1, but not Akt2, phosphorylates EMSY at Ser209, relieving EMSY-mediated ISG repression. The Akt1/EMSY/ISG pathway is activated by both viral infection and IFN, and it inhibits the replication of HSV-1 and vesicular stomatitis virus (VSV). Collectively, these data define an Akt1-dependent pathway that contributes to the full activation of ISGs by relieving their repression by EMSY and BRCA2.
Ezell et al. (Mon,) conducted a other in Viral infection. Akt1 phosphorylation of EMSY was evaluated on Interferon-stimulated gene (ISG) expression and viral replication. Akt1 phosphorylates the transcriptional repressor EMSY, relieving its repression of interferon-stimulated genes and inhibiting the replication of HSV-1 and vesicular stomatitis virus.
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