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We previously recognized PS1 mutants Lively in the absence of NCT [29]. These mutants possessed two missense mutations in PS1: S438P in the ninth transmembrane domain along with just one mutation distributed through the entire molecule. These PS1 mutations enhanced and modulated the γ-secretase activity and diminished the ratio of long Aβs [32]. We then isolated Aph1 or Pen2 mutants able to develop in the absence of NCT. After we experienced screened cells with Pen2 or Aph1 mutations plus the PS1 S438P mutation, we located thirteen Aph1 mutants that grew inside the absence of NCT (desk 1 and Figure 1).
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