@article{d46b01e323ee478688c6cd357890f79a,
title = "Lysosomal activity maintains glycolysis and cyclin E1 expression by mediating Ad4BP/SF-1 stability for proper steroidogenic cell growth",
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 Huang, {Bu Miin} and Lu, {Fu I.} and Wang, {Chia Yih}",
note = "Funding Information: We thank Dr. Bon-chu Chung for providing Ad4BP/SF-1 constructs; Dr. Yang-Kao Wang for providing sodium pyruvate; Dr. Yi-wen Liu for providing Ff1b construct. We acknowledge the TZCF(Taiwan Zebrafish Core Facility) which is supported by grant 104-2319-B-400-001 from Ministry of Science and Technology (MOST), Taiwan for the zebrafish whole mount in situ hybridization service. We are grateful for the support from the Core Research Laboratory, College of Medicine, National Cheng Kung University. RNAi reagents were obtained from the National Core Facility for Manipulation of Gene Function by RNAi, miRNA, miRNA sponges, and CRISPR/Genomic Research Center, Academia Sinica, supported by the National Core Facility Program for Biotechnology Grants of MOST (MOST 104-2319-B-001-001-). This study was supported by grant from Ministry of Science and Technology, MOST103-2628-B-006-001-MY3 and MOST104-2314-B-006-002 to Chia-Yih Wang; MOST103-2313-B-006-006 and MOST104-2311-B-006-005-MY3 to Fu-I Lu. This research was, in part, supported by the Ministry of Education, Taiwan, ROC. The Aim for the Top University Project to the National Cheng Kung University (NCKU). This research received funding from the Headquarters of University Advancement at the National Cheng Kung University, which is sponsored by the Ministry of Education, Taiwan, ROC. This research was supported in part by (received funding from) the Headquarters of University Advancement at the National Cheng Kung University, which is sponsored by the Ministry of Education, Taiwan, ROC. Funding Information: We thank Dr. Bon-chu Chung for providing Ad4BP/SF-1 constructs; Dr. Yang-Kao Wang for providing sodium pyruvate; Dr. Yi-wen Liu for providing Ff1b construct. We acknowledge the TZCF(Taiwan Zebrafish Core Facility) which is supported by grant 104-2319-B-400 -001 from Ministry of Science and Technology (MOST), Taiwan for the zebrafish whole mount in situ hybridization service. We are grateful for the support from the Core Research Laboratory, College of Medicine, National Cheng Kung University. RNAi reagents were obtained from the National Core Facility for Manipulation of Gene Function by RNAi, miRNA, miRNA sponges, and CRISPR/Genomic Research Center, Academia Sinica, supported by the National Core Facility Program for Biotechnology Grants of MOST (MOST 104-2319-B-001-001 -). This study was supported by grant from Ministry of Science and Technology, MOST103-2628-B-006-001-MY3 and MOST104-2314-B-006-002 to Chia-Yih Wang; MOST103-2313-B-006-006 and MOST104-2311-B-006-005-MY3 to Fu-I Lu. This research was, in part, supported by the Ministry of Education, Taiwan, ROC. The Aim for the Top University Project to the National Cheng Kung University (NCKU). This research received funding from the Headquarters of University Advancement at the National Cheng Kung University, which is sponsored by the Ministry of Education, Taiwan, ROC. This research was supported in part by (received funding from) the Headquarters of University Advancement at the National Cheng Kung University, which is sponsored by the Ministry of Education, Taiwan, ROC. Publisher Copyright: {\textcopyright} The Author(s) 2017.",
year = "2017",
doi = "10.1038/s41598-017-00393-4",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}