A Regulation Loop between YAP and NR4A1 Balances Cell Proliferation and Apoptosis
Summary: The Hippo signaling pathway maintains organ size and tissue homeostasis via orchestration of cell proliferation and apoptosis. How this pathway triggers cell apoptosis remains largely unexplored. Here, we identify NR4A1 as a target of the Hippo pathway that mediates the pro-apoptotic and an...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-10-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720312730 |
| _version_ | 1811294243384197120 |
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| author | Lingli He Liang Yuan Wentao Yu Yang Sun Dan Jiang Xiaodong Wang Xue Feng Zuoyun Wang Jinjin Xu Ruizeng Yang Wenxiang Zhang Hua Feng Hang-zi Chen Yi Arial Zeng Lijian Hui Qiao Wu Yonglong Zhang Lei Zhang |
| author_facet | Lingli He Liang Yuan Wentao Yu Yang Sun Dan Jiang Xiaodong Wang Xue Feng Zuoyun Wang Jinjin Xu Ruizeng Yang Wenxiang Zhang Hua Feng Hang-zi Chen Yi Arial Zeng Lijian Hui Qiao Wu Yonglong Zhang Lei Zhang |
| author_sort | Lingli He |
| collection | DOAJ |
| description | Summary: The Hippo signaling pathway maintains organ size and tissue homeostasis via orchestration of cell proliferation and apoptosis. How this pathway triggers cell apoptosis remains largely unexplored. Here, we identify NR4A1 as a target of the Hippo pathway that mediates the pro-apoptotic and anti-tumor effects of the Hippo pathway whereby YAP regulates the transcription, phosphorylation, and mitochondrial localization of NR4A1. NR4A1, in turn, functions as a feedback inhibitor of YAP to promote its degradation, thereby inhibiting the function of YAP during liver regeneration and tumorigenesis. Our studies elucidate a regulatory loop between NR4A1 and YAP to coordinate Hippo signaling activity during liver regeneration and tumorigenesis and highlight NR4A1 as a marker of Hippo signaling, as well as a therapeutic target for hepatocellular carcinoma. |
| first_indexed | 2024-04-13T05:13:36Z |
| format | Article |
| id | doaj.art-3073b7c2389a4f9a8a749e7f97c29550 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T05:13:36Z |
| publishDate | 2020-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-3073b7c2389a4f9a8a749e7f97c295502022-12-22T03:00:57ZengElsevierCell Reports2211-12472020-10-01333108284A Regulation Loop between YAP and NR4A1 Balances Cell Proliferation and ApoptosisLingli He0Liang Yuan1Wentao Yu2Yang Sun3Dan Jiang4Xiaodong Wang5Xue Feng6Zuoyun Wang7Jinjin Xu8Ruizeng Yang9Wenxiang Zhang10Hua Feng11Hang-zi Chen12Yi Arial Zeng13Lijian Hui14Qiao Wu15Yonglong Zhang16Lei Zhang17State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai 201210, ChinaState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, ChinaState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, ChinaState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai 201210, ChinaState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, ChinaState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, ChinaState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, ChinaState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, ChinaState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, ChinaOmics Core of Bio-Med Big Data Center, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian Province, ChinaState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, ChinaState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian Province, ChinaState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Corresponding authorState Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Bio-Research Innovation Center, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Suzhou 215121, China; Corresponding authorSummary: The Hippo signaling pathway maintains organ size and tissue homeostasis via orchestration of cell proliferation and apoptosis. How this pathway triggers cell apoptosis remains largely unexplored. Here, we identify NR4A1 as a target of the Hippo pathway that mediates the pro-apoptotic and anti-tumor effects of the Hippo pathway whereby YAP regulates the transcription, phosphorylation, and mitochondrial localization of NR4A1. NR4A1, in turn, functions as a feedback inhibitor of YAP to promote its degradation, thereby inhibiting the function of YAP during liver regeneration and tumorigenesis. Our studies elucidate a regulatory loop between NR4A1 and YAP to coordinate Hippo signaling activity during liver regeneration and tumorigenesis and highlight NR4A1 as a marker of Hippo signaling, as well as a therapeutic target for hepatocellular carcinoma.http://www.sciencedirect.com/science/article/pii/S2211124720312730Hippo signaling pathwayNR4A1apoptosisliver regenerationhepatocellular carcinoma (HCC) |
| spellingShingle | Lingli He Liang Yuan Wentao Yu Yang Sun Dan Jiang Xiaodong Wang Xue Feng Zuoyun Wang Jinjin Xu Ruizeng Yang Wenxiang Zhang Hua Feng Hang-zi Chen Yi Arial Zeng Lijian Hui Qiao Wu Yonglong Zhang Lei Zhang A Regulation Loop between YAP and NR4A1 Balances Cell Proliferation and Apoptosis Cell Reports Hippo signaling pathway NR4A1 apoptosis liver regeneration hepatocellular carcinoma (HCC) |
| title | A Regulation Loop between YAP and NR4A1 Balances Cell Proliferation and Apoptosis |
| title_full | A Regulation Loop between YAP and NR4A1 Balances Cell Proliferation and Apoptosis |
| title_fullStr | A Regulation Loop between YAP and NR4A1 Balances Cell Proliferation and Apoptosis |
| title_full_unstemmed | A Regulation Loop between YAP and NR4A1 Balances Cell Proliferation and Apoptosis |
| title_short | A Regulation Loop between YAP and NR4A1 Balances Cell Proliferation and Apoptosis |
| title_sort | regulation loop between yap and nr4a1 balances cell proliferation and apoptosis |
| topic | Hippo signaling pathway NR4A1 apoptosis liver regeneration hepatocellular carcinoma (HCC) |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720312730 |
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