Lysosomal activity maintains glycolysis and cyclin E1 expression by controlling Ad4BP/SF-1 stability for proper steroidogenic cell growth

• Main Authors: Jhih-SiangSyu, 許志祥
• Other Authors: Chia-Yih Wang
• Format: Others
• Language: en_US
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/z8yhud

碩士 === 國立成功大學 === 細胞生物與解剖學研究所 === 104 === The development and differentiation of steroidogenic organs are controlled by Ad4BP/SF-1 (adrenal 4 binding protein/steroidogenic factor 1). Besides, lysosomal activity is required for steroidogenesis and also enables adrenocortical cell to survive during stress. However, the role of lysosomal activity on steroidogenic cell growth is as yet unknown. Here, we showed that lysosomal activity maintained Ad4BP/SF-1 protein stability for proper steroidogenic cell growth. Treatment of cells with lysosomal inhibitors reduced steroidogenic cell growth in vitro. Suppression of autophagy did not affect cell growth indicating that autophagy was dispensable for steroidogenic cell growth. When lysosomal activity was inhibited, the protein stability of Ad4BP/SF-1 was reduced leading to G1 arrest. Interestingly, treatment of cell with lysosomal inhibitor reduced glycolytic genes expression and supplying the cells with pyruvate alleviated the growth defect. ChIP-sequence/ChIP studies indicated that Ad4BP/SF-1 binds to the upstream region of Ccne1 (cyclin E1) gene during G1/S phase. In addition, treatment of zebrafish embryo with lysosomal inhibitor reduced the growth of the interrenal (adrenal) gland in vivo. Thus lysosomal activity maintains steroidogenic cell growth via stabilizing Ad4BP/SF-1.