FIGURE 8:

PERK and ATF4 facilitate increased expression of the ATF6 gene in response to ER stress. (A) WT MEF cells were treated with tunicamycin (TUN), 10 μM actinomycin D and tunicamycin (AD/TUN), or actinomycin D (AD) alone for up to 6 h, as indicated. The levels of ATF6-FL/G, ATF6-FL/UG, and actin were measured by immunoblot analysis. (B) PERK^−/− and ATF4^−/− MEF cells, and their WT counterparts, were treated with tunicamycin for up to 6 h, and the levels of ATF6 mRNA were measured by qPCR. (C) A 1.5-kb segment (−1500 to −1) of the ATF6 promoter was fused to a firefly luciferase reporter and assayed for expression in MEF cells treated with either tunicamycin for 6 h or no stress agent. The fold change in ATF6 promoter activity in response to ER stress was determined by the dual luciferase assay. In panels B and C, the error bar represents the SD, and the * indicates significance between untreated and treated samples; the # indicates significance between cell types, with p < 0.05.