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SUMOylation of BACE1 at K501 increases its enzymatic activity. (A and B) FLAG-BACE1 WT plus UBC9 or different lysine residue mutant (K275R and K501R) plasmids plus UBC9 were cotransfected to N2A/APP cells for 48 h; next, the secreted fragment APP-β cleaved by BACE1 and the total APP in lysate were examined by Western blotting and quantitative analysis. (C and D) The Aβ40 and Aβ42 levels in cell medium were measured by ELISA. **P < 0.01 vs. vector; ##P < 0.01 vs. BACE1 WT.
