Title Page
Abstract
Contents
Introduction 11
1. Role of PS on substrate specificity of γ-secretase 12
2. Role of PS for regulation of β-catenin 19
Materials and Methods 24
Results 33
1. Role of PS on substrate specificity of γ-secretase 33
2. Role of PS for regulation of β-catenin 46
Discussion 63
1. Role of PS on substrate specificity of γ-secretase 63
2. Role of PS for regulation of β-catenin 68
References 75
국문 초록 93
Figure 1. APP processing (Sangram S. Sisodia and Peter H. St... 16
Figure 2. Aβ generation by normal proteolytic processing of APP 17
Figure 3. Schematic diagram of PS1 18
Figure 4. Wnt/β-catenin signaling (Randall T. Moon and et al.,... 23
Figure 5. Schematic diagram of luciferase reporter gene assay... 32
Figure 6. Constitutively active form and dominant-negative form of... 38
Figure 7. Rac1 inhibitor altered the production of AICD and NICD in... 41
Figure 8. Inactive Rac1 strongly interacted with PS1. 44
Figure 9. Rac1 inhibitor regulated the affinity of PS1 to APP and... 45
Figure 10. PS dKO MEFs are vulnerable to serum deprivation-... 51
Figure 11. ROS-mediated serum deprivation-induced cell death in... 54
Figure 12. Phospho-β-catenin accumulates in PS dKO MEFs under... 58
Figure 13. Accumulation of phospho-β-catenin induces cytotoxicity... 60
Figure 14. Phospho-β-catenin was detected in cerebral cortex of... 62
Figure 15. Activation status of Rac1 might regulate the substrate... 67
Figure 16. Roles of PS in serum deprivation-induced cell death. 74