REA translocates from cytoplasm to nuclear and functions as a repressor of BACE1 promoter activity in the presence of E2 in SH-SY5Y cells. A, REA is primarily located in the cytoplasm of SY5Y cells, where they colocalize with Mito-tracker Red when treated with vehicle. B, Part of REA translocates to the nuclear when treated with 100 nm E2 in SY5Y cells. C, D, E2 treatment induces the translocation of REA from cytoplasm to nuclear in an E2 dosage-dependent manner in SH-SY5Y cells. E, E2 treatment induced translocation of REA from the cytoplasm to the nuclear in the mouse brain. F, REA was knocked down using two different siRNAs (siREA-1 and siREA-2) in stable HEK293 cell lines with BACE1 wild-type promoters. The cells transiently transfected with siREA-2 and si-control (Si-CON) were treated with estrogen, with TNFα as a positive control. REA knockdown attenuated the E2-mediated repression of BACE1 promoter activity. Data are expressed as a percentage of control in each experiment and are represented as the mean SEM of at least three independent experiments. **p < 0.01. Veh, Vehicle.