Figure 4.

IFN suppression by Nogo is independent of the Ras/ERK pathway. (A and B) Enhancement of IFN response in Ras-transformed cells by MEK inhibitor (U0126) was compared between control and Nogo-KD cells. Cells were infected with increasing doses of reoviruses (MOI of 200 or 400 based on their titers in L929 cells) in the presence or absence of U0126 (10 μM). Data are presented as mean values with error bars showing the standard deviations. (C) Nogo-B cleavage was analyzed by western blot in cells treated with U0126 (10 μM) for 18 hr. (D) Schematic diagram of the proposed model. Ras-transformation suppresses IFN signaling by 2 separate but cooperative mechanisms, with the Ras/ERK and Nogo-B cleavage pathways representing the major and minor IFN inhibitory pathways, respectively.