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

摘要

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

獎項日期	2016 8月 11
原文	English
監督員	Chia-Yih Wang (Supervisor)