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

Autor: Jeong-Ryul Hwang, Donghwan Kim, Jung-Ah Kang, Sang-Heon Park, Sung-Gyoo Park
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Scientific Reports, Vol 13, Iss 1, Pp 1-10 (2023)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-022-26674-1
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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