Transcriptional regulation of Notch1 by nuclear factor-κB during T cell activation

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Transcriptional regulation of Notch1 by nuclear factor-κB during T cell activation
J R Hwang; D Kim; Jung-Ah Kang; S H Park; S G Park
Bibliographic Citation
Scientific Reports, vol. 13, pp. 43-43
Publication Year
Notch1 plays important roles in T cell development and is highly expressed in activated CD4+ T cells. However, the underlying mechanism of Notch1 transcription in T cells has not been fully characterized. Therefore, we aimed to determine how Notch1 expression is regulated during the activation of CD4+ T cells. Both the surface expression and mRNA transcription of Notch1 were significantly higher in activated CD4+ T cells, but the inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 or deletion of the Pdk1 gene impaired this upregulation of Notch1. Interrogation of the Notch1 promoter region using serially deleted Notch1 promoter reporters revealed that the - 300 to - 270 region is crucial for its transcription in activated T cells. In addition, we found that nuclear factor (NF)-κB subunits containing RelA bind directly to this promoter region, thereby upregulating transcription. In addition, inhibition of NF-κB by SN50 impaired upregulation of Notch1 surface protein and mRNA in activated CD4+ T cells. Thus, we provide evidence that Notch1 transcription in activated CD4+ T cells is upregulated via the PI3K-PDK1-NF-κB signaling pathway.
Springer-Nature Pub Group
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Division of Research on National Challenges > Bionanotechnology Research Center > 1. Journal Articles
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