Survivin Blocks Smac/DIABLO Releasing from Mitochondria to Prevent 5-Fluorouracil Induced Apoptosis

• Main Authors: Po-Hao Chang, 張博皓
• Other Authors: Fen-Hwa Wong
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/64565556922178245501

碩士 === 國立陽明大學 === 生命科學暨基因體科學研究所 === 95 === Survivin is a bifunctional protein and participates in cell division and cell-death inhibition. In cell division, it associates with INCENP, Aurora B and Borealin to form the chromosomal passenger complex. The complex is required to target to kinetochores, correct misaligned chromosomes and complete cytokinesis. In cell-death inhibition, Survivin has a single Baculovirus IAP Repeat (BIR) domain and belonged to inhibitor of apoptosis proteins (IAPs) family. However, its inhibitory mechanism remains controversial. In this study, it was demonstrated that 5-fluorouracil (5-Fu) induced apoptosis through the intrinsic apoptosis pathway, mediates cytochrome c and Smac/DIABLO releasing from mitochondria into cytosol and activates caspase-9 and caspase-3. Overexpression of Survivin protects esophageal carcinoma cells (CE cells) from 5-Fu induced apoptosis, and Survivin prevents Smac/DIABLO release from mitochondria. In addition, co-expression of Survivin and Smac/DIABLO is redundant for cytosolic Smac/DIABLO-mediated apoptosis. These results indicated that Survivin protects 5-Fu-induced apoptosis by preventing Smac/DIABLO released from mitochondria which in turn inhibits caspase-3 and caspase-9 activation.