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 lysoso...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-00393-4 |
| _version_ | 1818420132124295168 |
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| author | 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-l. Lu Chia-Yih Wang |
| author_facet | 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-l. Lu Chia-Yih Wang |
| author_sort | Jhih-Siang Syu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T12:49:36Z |
| format | Article |
| id | doaj.art-35ade0a21f8d4166b02d00fb684be8c8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T12:49:36Z |
| publishDate | 2017-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-35ade0a21f8d4166b02d00fb684be8c82022-12-21T23:00:42ZengNature PortfolioScientific Reports2045-23222017-03-017111410.1038/s41598-017-00393-4Lysosomal activity maintains glycolysis and cyclin E1 expression by mediating Ad4BP/SF-1 stability for proper steroidogenic cell growthJhih-Siang Syu0Takashi Baba1Jyun-Yuan Huang2Hidesato Ogawa3Chi-Han Hsieh4Jin-Xian Hu5Ting-Yu Chen6Tzu-Chien Lin7Megumi Tsuchiya8Ken-Ichirou Morohashi9Bu-Miin Huang10Fu-l. Lu11Chia-Yih Wang12Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung UniversityDivision of Molecular Life Science, Graduate School of Systems Life Science, Kyushu UniversityDivision of Genetics, Department of Obstetrics and Gynecology, National Cheng Kung University HospitalAdvanced ICT Research Institute Kobe, National Institute of Information and Communications TechnologyDepartment of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung UniversityDepartment of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung UniversityDepartment of Cell Biology and Anatomy, College of Medicine, National Cheng Kung UniversityDepartment of Cell Biology and Anatomy, College of Medicine, National Cheng Kung UniversityGraduate School of Frontier Biosciences, Osaka UniversityDivision of Molecular Life Science, Graduate School of Systems Life Science, Kyushu UniversityDepartment of Cell Biology and Anatomy, College of Medicine, National Cheng Kung UniversityDepartment of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung UniversityDepartment of Cell Biology and Anatomy, College of Medicine, National Cheng Kung UniversityAbstract 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.https://doi.org/10.1038/s41598-017-00393-4 |
| spellingShingle | 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-l. Lu Chia-Yih Wang Lysosomal activity maintains glycolysis and cyclin E1 expression by mediating Ad4BP/SF-1 stability for proper steroidogenic cell growth Scientific Reports |
| title | Lysosomal activity maintains glycolysis and cyclin E1 expression by mediating Ad4BP/SF-1 stability for proper steroidogenic cell growth |
| title_full | Lysosomal activity maintains glycolysis and cyclin E1 expression by mediating Ad4BP/SF-1 stability for proper steroidogenic cell growth |
| title_fullStr | Lysosomal activity maintains glycolysis and cyclin E1 expression by mediating Ad4BP/SF-1 stability for proper steroidogenic cell growth |
| title_full_unstemmed | Lysosomal activity maintains glycolysis and cyclin E1 expression by mediating Ad4BP/SF-1 stability for proper steroidogenic cell growth |
| title_short | Lysosomal activity maintains glycolysis and cyclin E1 expression by mediating Ad4BP/SF-1 stability for proper steroidogenic cell growth |
| title_sort | lysosomal activity maintains glycolysis and cyclin e1 expression by mediating ad4bp sf 1 stability for proper steroidogenic cell growth |
| url | https://doi.org/10.1038/s41598-017-00393-4 |
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