Title Page
Contents
Abstract 10
1. Introduction 14
2. Materials and Methods 25
Cell Culture 25
Transfection 26
Western Blot Analysis 27
Cell viability assay 28
Immunocytochemistry 29
Statistical Analysis 30
3. Results 31
3.1. Correlation of the AGR2 and autophagy 31
3.2. AGR2 is not a degradation substrate at the basal level 35
3.3. AGR2 is a proteasomal and autophagic substrate in ER stress condition 38
3.4. AGR2 has a degradation signal that calls N-degron 41
3.5. AGR2 is upregulated by inhibition of the Arg/N-terminal pathway 43
3.6. AGR2 enhances cell survival under ER stress 46
3.7. AGR2 enhances cell survival under ER stress via autophagy 48
4. Discussion 50
5. Reference 53
6. 국문요약 65
Figure 1. AGR2 protein architecture 16
Figure 2. Emerging roles of AGR2 protein in cancer 20
Figure 3. Post-translational arginylation 23
Figure 4. AGR2 knock-down upregulates autophagy markers 32
Figure 5. AGR2 knock-down cells have many p62 dots stain more than the MCF7 control 34
Figure 6. The effect of proteasome or autophagy inhibitor in MCF7 37
Figure 7. The effect of proteasome or autophagy inhibitor in MCF7under ER stress 40
Figure 8. Tannic acid suppresses AGR2 degradation flux 42
Figure 9. AGR2 is degraded by the Arg/N-terminal pathway 45
Figure 10. Cell viability in MCF7 and AGR2 knock-down under ER stress 47
Figure 11. Cell viability in MCF7 and AGR2 knock-down with thapsigargin and tannic acid 49