Cancers, Vol. 10, Pages 119: NF- κB Signaling Regulates Epstein–Barr Virus BamHI-Q-Driven EBNA1 Expression

Cancers, Vol. 10, Pages 119: NF-κB Signaling Regulates Epstein–Barr Virus BamHI-Q-Driven EBNA1 Expression Cancers doi: 10.3390/cancers10040119 Authors: Rob Verhoeven Shuang Tong Jingfeng Zong Yixin Chen Sai-Wah Tsao Jianji Pan Honglin Chen Epstein–Barr virus (EBV) nuclear antigen 1 (EBNA1) is one of the few viral proteins expressed by EBV in nasopharyngeal carcinoma (NPC), most likely because of its essential role in maintaining the viral genome in EBV-infected cells. In NPC, EBNA1 expression is driven by the BamHI-Q promoter (Qp), which is regulated by both cellular and viral factors. We previously determined that the expression of another group of EBV transcripts, BamHI-A rightward transcripts (BARTs), is associated with constitutively activated nuclear factor-κB (NF-κB) signaling in NPC cells. Here, we show that, like the EBV BART promoter, the EBV Qp also responds to NF-κB signaling. NF-κB p65, but not p50, can activate Qp in vitro, and NF-κB signaling regulates Qp-EBNA1 expression in NPC cells, as well as in other EBV-infected epithelial cells. The introduction of mutations in the putative NF-κB site reduced Qp activation by the NF-κB p65 subunit. Binding of p65 to Qp was shown by chromatin immunoprecipitation (ChIP) analysis, while electrophoretic mobility shift assays (EMSAs) demonstrated that p50 can also bind to Qp. Inhibition of NF-κB signaling by the IκB kinase inhibitor PS-1145 resulted in the downregulation of Qp-EBNA1 expression...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research