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. 2009 Apr 3;284(14):9027–9038. doi: 10.1074/jbc.M805685200

FIGURE 4.

FIGURE 4.

The up-regulation of BACE1 induced by PS1 mutations requires the activity of the γ-secretase. A, HEK-293 APPwt cells were treated with a transition analogue inhibitor of γ-secretase at the moment of transfection with empty vector control, PS1 wild type, and PS1 S170F and replenished twice every 4 h; BACE1 protein levels were analyzed. B, MEFs PS1–/– were treated similarly, and BACE1 protein levels were analyzed. Basal levels of BACE1 mRNA (C), protein levels (D), and activity (E) were evaluated in MEFs PS1–/–, all resulting lower than in wild type cells. F, MEFs deficient for both PS1 and PS2 were transfected with empty vector control or with PS1 and PS2: reconstitution of PS1/2 expression determined an increased expression of BACE1; PS1/2 CTFs are produced as expected. Data represent the mean and S.E. of three or more experiments; significance is relative to the empty vector control or to control cells. Statistical analysis was performed with ANOVA (A and B) and Bonferroni post-test and t test (C–F).