Loss of TBP function causes apoptosis due to oxidative stress and p53 activation in Drosophila melanogaster

• Main Authors: Chin-Sern Yong, 楊進勝
• Other Authors: Ming-Tsan Su
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/50816922701064508299

碩士 === 國立臺灣師範大學 === 生命科學研究所 === 101 === Previous studies revealed that loss of TBP function causes developmental arrest and apoptosis in mice and zebrafish. How TBP regulates animal development and apoptosis is currently elusive. The main objectives of this study are to test whether function of Drosophila TBP (dTbp) in regulating apoptosis is conserved, and to dissect the mechanisms by which dTbp regulates apoptotic pathway. We find that homozygous dTbp mutant flies die during late embryogenesis, and ectopic cell death was observed in the dying embryos. Somatic clone analysis reveals that loss of dTbp causes apoptosis in a cell autonomous manner. In genetic analyses, we find that ectopic expression of dominant negative P53 (P53DN) or DIAP1 can suppress deactivated dTbp induced cell death, indicating dTbp is a member of P53 mediated apoptotic pathway. We also find that total protein and ribonucleic acid are not reduced significantly in dTbp mutant flies, suggesting that dTbp might affect only a few genes to regulate apoptosis. Through gene profiling experiments, we find that the expression of Prx2540-2 is greatly reduced in dTbp mutants. Prx normally reduces hydrogen peroxide, and can protect cells from oxidative stress. In our preliminary studies, we find that H2O2 is higher in dTbp mutant flies, and antioxidants can extend the lifespan of dTbp mutants. In sum, our result suggests that activation of P53 and oxidative stress contribute to deactivated dTbp induced apoptosis.