The Ets Transcription Factor GABP Is a Component of the Hippo Pathway Essential for Growth and Antioxidant Defense
The transcriptional coactivator Yes-associated protein (YAP) plays an important role in organ-size control and tumorigenesis. However, how Yap gene expression is regulated remains unknown. This study shows that the Ets family member GABP binds to the Yap promoter and activates YAP transcription. The...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2013-05-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713002027 |
| _version_ | 1818835797291302912 |
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| author | Hongtan Wu Yubo Xiao Shihao Zhang Suyuan Ji Luyao Wei Fuqin Fan Jing Geng Jing Tian Xiufeng Sun Funiu Qin Changnan Jin Jianjun Lin Zhen-Yu Yin Ting Zhang Lianzhong Luo Yang Li Siyang Song Sheng-Cai Lin Xianming Deng Fernando Camargo Joseph Avruch Lanfen Chen Dawang Zhou |
| author_facet | Hongtan Wu Yubo Xiao Shihao Zhang Suyuan Ji Luyao Wei Fuqin Fan Jing Geng Jing Tian Xiufeng Sun Funiu Qin Changnan Jin Jianjun Lin Zhen-Yu Yin Ting Zhang Lianzhong Luo Yang Li Siyang Song Sheng-Cai Lin Xianming Deng Fernando Camargo Joseph Avruch Lanfen Chen Dawang Zhou |
| author_sort | Hongtan Wu |
| collection | DOAJ |
| description | The transcriptional coactivator Yes-associated protein (YAP) plays an important role in organ-size control and tumorigenesis. However, how Yap gene expression is regulated remains unknown. This study shows that the Ets family member GABP binds to the Yap promoter and activates YAP transcription. The depletion of GABP downregulates YAP, resulting in a G1/S cell-cycle block and increased cell death, both of which are substantially rescued by reconstituting YAP. GABP can be inactivated by oxidative mechanisms, and acetaminophen-induced glutathione depletion inhibits GABP transcriptional activity and depletes YAP. In contrast, activating YAP by deleting Mst1/Mst2 strongly protects against acetaminophen-induced liver injury. Similar to its effects on YAP, Hippo signaling inhibits GABP transcriptional activity through several mechanisms. In human liver cancers, enhanced YAP expression is correlated with increased nuclear expression of GABP. Therefore, we conclude that GABP is an activator of Yap gene expression and a potential therapeutic target for cancers driven by YAP. |
| first_indexed | 2024-12-19T02:56:25Z |
| format | Article |
| id | doaj.art-1e54d500f5d0467985130d2f25e9acde |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-19T02:56:25Z |
| publishDate | 2013-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-1e54d500f5d0467985130d2f25e9acde2022-12-21T20:38:19ZengElsevierCell Reports2211-12472013-05-01351663167710.1016/j.celrep.2013.04.020The Ets Transcription Factor GABP Is a Component of the Hippo Pathway Essential for Growth and Antioxidant DefenseHongtan Wu0Yubo Xiao1Shihao Zhang2Suyuan Ji3Luyao Wei4Fuqin Fan5Jing Geng6Jing Tian7Xiufeng Sun8Funiu Qin9Changnan Jin10Jianjun Lin11Zhen-Yu Yin12Ting Zhang13Lianzhong Luo14Yang Li15Siyang Song16Sheng-Cai Lin17Xianming Deng18Fernando Camargo19Joseph Avruch20Lanfen Chen21Dawang Zhou22State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiang’an District, Xiamen, Fujian 361102, ChinaState Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiang’an District, Xiamen, Fujian 361102, ChinaState Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiang’an District, Xiamen, Fujian 361102, ChinaState Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiang’an District, Xiamen, Fujian 361102, ChinaState Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiang’an District, Xiamen, Fujian 361102, ChinaState Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiang’an District, Xiamen, Fujian 361102, ChinaState Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiang’an District, Xiamen, Fujian 361102, ChinaState Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiang’an District, Xiamen, Fujian 361102, ChinaState Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiang’an District, Xiamen, Fujian 361102, ChinaState Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiang’an District, Xiamen, Fujian 361102, ChinaDepartment of Hepatology, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian 361001, ChinaDepartment of Hepatology, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian 361001, ChinaDepartment of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian 361004, ChinaDepartment of Hepatology, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian 361001, ChinaDepartment of Pharmacy, Xiamen Medical College, Xiamen, Fujian 361008, ChinaState Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiang’an District, Xiamen, Fujian 361102, ChinaState Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiang’an District, Xiamen, Fujian 361102, ChinaState Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiang’an District, Xiamen, Fujian 361102, ChinaState Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiang’an District, Xiamen, Fujian 361102, ChinaStem Cell Program, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Molecular Biology, Diabetes Unit, Medical Services, Massachusetts General Hospital, Boston, MA 02114, USAState Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiang’an District, Xiamen, Fujian 361102, ChinaState Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiang’an District, Xiamen, Fujian 361102, ChinaThe transcriptional coactivator Yes-associated protein (YAP) plays an important role in organ-size control and tumorigenesis. However, how Yap gene expression is regulated remains unknown. This study shows that the Ets family member GABP binds to the Yap promoter and activates YAP transcription. The depletion of GABP downregulates YAP, resulting in a G1/S cell-cycle block and increased cell death, both of which are substantially rescued by reconstituting YAP. GABP can be inactivated by oxidative mechanisms, and acetaminophen-induced glutathione depletion inhibits GABP transcriptional activity and depletes YAP. In contrast, activating YAP by deleting Mst1/Mst2 strongly protects against acetaminophen-induced liver injury. Similar to its effects on YAP, Hippo signaling inhibits GABP transcriptional activity through several mechanisms. In human liver cancers, enhanced YAP expression is correlated with increased nuclear expression of GABP. Therefore, we conclude that GABP is an activator of Yap gene expression and a potential therapeutic target for cancers driven by YAP.http://www.sciencedirect.com/science/article/pii/S2211124713002027 |
| spellingShingle | Hongtan Wu Yubo Xiao Shihao Zhang Suyuan Ji Luyao Wei Fuqin Fan Jing Geng Jing Tian Xiufeng Sun Funiu Qin Changnan Jin Jianjun Lin Zhen-Yu Yin Ting Zhang Lianzhong Luo Yang Li Siyang Song Sheng-Cai Lin Xianming Deng Fernando Camargo Joseph Avruch Lanfen Chen Dawang Zhou The Ets Transcription Factor GABP Is a Component of the Hippo Pathway Essential for Growth and Antioxidant Defense Cell Reports |
| title | The Ets Transcription Factor GABP Is a Component of the Hippo Pathway Essential for Growth and Antioxidant Defense |
| title_full | The Ets Transcription Factor GABP Is a Component of the Hippo Pathway Essential for Growth and Antioxidant Defense |
| title_fullStr | The Ets Transcription Factor GABP Is a Component of the Hippo Pathway Essential for Growth and Antioxidant Defense |
| title_full_unstemmed | The Ets Transcription Factor GABP Is a Component of the Hippo Pathway Essential for Growth and Antioxidant Defense |
| title_short | The Ets Transcription Factor GABP Is a Component of the Hippo Pathway Essential for Growth and Antioxidant Defense |
| title_sort | ets transcription factor gabp is a component of the hippo pathway essential for growth and antioxidant defense |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713002027 |
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