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

Jhih Siang Syu, Takashi Baba, Jyun Yuan Huang, Hidesato Ogawa, Chi Han Hsieh, Jin Xian Hu, Ting Yu Chen, Tzu Chien Lin, Megumi Tsuchiya, Ken Ichirou Morohashi, Bu-Miin Huang, Fu-I Lu, Chia-Yih Wang

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Abstract

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 reduced S phase entry. Interestingly, treatment of cells with lysosomal inhibitors reduced glycolytic gene 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 levels of the interrenal (adrenal) gland markers. Thus lysosomal activity maintains steroidogenic cell growth via stabilizing Ad4BP/SF-1 protein.

Original languageEnglish
Article number240
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Jan 1

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Steroidogenic Factor 1
Cyclins
Glycolysis
Growth
Protein Stability
Autophagy
S Phase
Interrenal Gland
G1 Phase
Zebrafish
Adrenal Glands
Pyruvic Acid
Embryonic Structures

All Science Journal Classification (ASJC) codes

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Syu, Jhih Siang ; Baba, Takashi ; Huang, Jyun Yuan ; Ogawa, Hidesato ; Hsieh, Chi Han ; Hu, Jin Xian ; Chen, Ting Yu ; Lin, Tzu Chien ; Tsuchiya, Megumi ; Morohashi, Ken Ichirou ; Huang, Bu-Miin ; Lu, Fu-I ; Wang, Chia-Yih. / Lysosomal activity maintains glycolysis and cyclin E1 expression by mediating Ad4BP/SF-1 stability for proper steroidogenic cell growth. In: Scientific reports. 2017 ; Vol. 7, No. 1.
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abstract = "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 reduced S phase entry. Interestingly, treatment of cells with lysosomal inhibitors reduced glycolytic gene 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 levels of the interrenal (adrenal) gland markers. Thus lysosomal activity maintains steroidogenic cell growth via stabilizing Ad4BP/SF-1 protein.",
author = "Syu, {Jhih Siang} and Takashi Baba and Huang, {Jyun Yuan} and Hidesato Ogawa and Hsieh, {Chi Han} and Hu, {Jin Xian} and Chen, {Ting Yu} and Lin, {Tzu Chien} and Megumi Tsuchiya and Morohashi, {Ken Ichirou} and Bu-Miin Huang and Fu-I Lu and Chia-Yih Wang",
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Lysosomal activity maintains glycolysis and cyclin E1 expression by mediating Ad4BP/SF-1 stability for proper steroidogenic cell growth. / Syu, Jhih Siang; Baba, Takashi; Huang, Jyun Yuan; Ogawa, Hidesato; Hsieh, Chi Han; Hu, Jin Xian; Chen, Ting Yu; Lin, Tzu Chien; Tsuchiya, Megumi; Morohashi, Ken Ichirou; Huang, Bu-Miin; Lu, Fu-I; Wang, Chia-Yih.

In: Scientific reports, Vol. 7, No. 1, 240, 01.01.2017.

Research output: Contribution to journalArticle

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T1 - Lysosomal activity maintains glycolysis and cyclin E1 expression by mediating Ad4BP/SF-1 stability for proper steroidogenic cell growth

AU - Syu, Jhih Siang

AU - Baba, Takashi

AU - Huang, Jyun Yuan

AU - Ogawa, Hidesato

AU - Hsieh, Chi Han

AU - Hu, Jin Xian

AU - Chen, Ting Yu

AU - Lin, Tzu Chien

AU - Tsuchiya, Megumi

AU - Morohashi, Ken Ichirou

AU - Huang, Bu-Miin

AU - Lu, Fu-I

AU - Wang, Chia-Yih

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Y1 - 2017/1/1

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