TFCP2 Is Required for YAP-Dependent Transcription to Stimulate Liver Malignancy
Summary: Although YAP-dependent transcription is closely associated with liver tumorigenesis, the mechanism by which YAP maintains its function is poorly understood. Here, we show that TFCP2 is required for YAP-dependent transcription and liver malignancy. Mechanistically, YAP function is stimulated...
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2017-10-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717314493 |
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doaj-553db43a831f446bb0d618e95424e92a2020-11-25T01:05:31ZengElsevierCell Reports2211-12472017-10-0121512271239TFCP2 Is Required for YAP-Dependent Transcription to Stimulate Liver MalignancyXiao Zhang0Fenyong Sun1Yongxia Qiao2Weisheng Zheng3Ya Liu4Yan Chen5Qi Wu6Xiangfan Liu7Guoqing Zhu8Yuxin Chen9Yongchun Yu10Qiuhui Pan11Jiayi Wang12Department of Clinical Laboratory, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072, ChinaDepartment of Clinical Laboratory, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072, ChinaSchool of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai 200025, ChinaSchool of Life Science and Technology, Shanghai Key Laboratory of Signaling and Disease Research, Tongji University, Shanghai 200092, ChinaDepartment of Clinical Laboratory, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072, ChinaDepartment of Clinical Laboratory, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072, ChinaDepartment of Clinical Laboratory, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072, ChinaFaculty of Medical Laboratory Science, Shanghai Jiaotong University School of Medicine, Shanghai 200025, ChinaDepartment of Clinical Laboratory, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072, ChinaDepartment of Clinical Laboratory, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072, ChinaShanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, ChinaDepartment of Laboratory Medicine, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China; Corresponding authorDepartment of Clinical Laboratory, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072, China; Advanced Institute of Translational Medicine, Tongji University, Shanghai 200092, China; Corresponding authorSummary: Although YAP-dependent transcription is closely associated with liver tumorigenesis, the mechanism by which YAP maintains its function is poorly understood. Here, we show that TFCP2 is required for YAP-dependent transcription and liver malignancy. Mechanistically, YAP function is stimulated by TFCP2 via a WW-PSY interaction. TFCP2 also maintains YAP stability by inhibiting βTrCP. Notably, genomic co-occupancy of YAP and TFCP2 is revealed. TFCP2 acts as a transcription co-factor that stimulates YAP transcription by facilitating YAP binding with YAP binding motif (YBF)-containing transcription factors. Interestingly, TFCP2 also stimulated the YAP-TEAD interaction and TEAD target gene expression. Finally, several genes co-regulated by YAP and TFCP2 that contribute to YAP-dependent tumorigenesis are identified and verified. Thus, we establish a model showing that TFCP2 acts as a YAP co-factor to maintain YAP-dependent transcription in liver cancer cells, suggesting that simultaneous targeting of both YAP and TFCP2 may be an effective therapeutic approach. : Zhang et al. reveal that TFCP2 acts as a YAP co-factor to stimulate YAP-dependent liver malignancy. YAP binds to TFCP2 via a WW-PSY interaction, which facilitates the binding of YAP to transcription factors that contain the YAP binding motif. These effects lead to the enhanced transcription of downstream co-regulated proto-oncogenes. Keywords: gene regulation, enhancer, YAP-dependent transcription factors, protein stability, βTrCPhttp://www.sciencedirect.com/science/article/pii/S2211124717314493 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Xiao Zhang Fenyong Sun Yongxia Qiao Weisheng Zheng Ya Liu Yan Chen Qi Wu Xiangfan Liu Guoqing Zhu Yuxin Chen Yongchun Yu Qiuhui Pan Jiayi Wang |
| spellingShingle |
Xiao Zhang Fenyong Sun Yongxia Qiao Weisheng Zheng Ya Liu Yan Chen Qi Wu Xiangfan Liu Guoqing Zhu Yuxin Chen Yongchun Yu Qiuhui Pan Jiayi Wang TFCP2 Is Required for YAP-Dependent Transcription to Stimulate Liver Malignancy Cell Reports |
| author_facet |
Xiao Zhang Fenyong Sun Yongxia Qiao Weisheng Zheng Ya Liu Yan Chen Qi Wu Xiangfan Liu Guoqing Zhu Yuxin Chen Yongchun Yu Qiuhui Pan Jiayi Wang |
| author_sort |
Xiao Zhang |
| title |
TFCP2 Is Required for YAP-Dependent Transcription to Stimulate Liver Malignancy |
| title_short |
TFCP2 Is Required for YAP-Dependent Transcription to Stimulate Liver Malignancy |
| title_full |
TFCP2 Is Required for YAP-Dependent Transcription to Stimulate Liver Malignancy |
| title_fullStr |
TFCP2 Is Required for YAP-Dependent Transcription to Stimulate Liver Malignancy |
| title_full_unstemmed |
TFCP2 Is Required for YAP-Dependent Transcription to Stimulate Liver Malignancy |
| title_sort |
tfcp2 is required for yap-dependent transcription to stimulate liver malignancy |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2017-10-01 |
| description |
Summary: Although YAP-dependent transcription is closely associated with liver tumorigenesis, the mechanism by which YAP maintains its function is poorly understood. Here, we show that TFCP2 is required for YAP-dependent transcription and liver malignancy. Mechanistically, YAP function is stimulated by TFCP2 via a WW-PSY interaction. TFCP2 also maintains YAP stability by inhibiting βTrCP. Notably, genomic co-occupancy of YAP and TFCP2 is revealed. TFCP2 acts as a transcription co-factor that stimulates YAP transcription by facilitating YAP binding with YAP binding motif (YBF)-containing transcription factors. Interestingly, TFCP2 also stimulated the YAP-TEAD interaction and TEAD target gene expression. Finally, several genes co-regulated by YAP and TFCP2 that contribute to YAP-dependent tumorigenesis are identified and verified. Thus, we establish a model showing that TFCP2 acts as a YAP co-factor to maintain YAP-dependent transcription in liver cancer cells, suggesting that simultaneous targeting of both YAP and TFCP2 may be an effective therapeutic approach. : Zhang et al. reveal that TFCP2 acts as a YAP co-factor to stimulate YAP-dependent liver malignancy. YAP binds to TFCP2 via a WW-PSY interaction, which facilitates the binding of YAP to transcription factors that contain the YAP binding motif. These effects lead to the enhanced transcription of downstream co-regulated proto-oncogenes. Keywords: gene regulation, enhancer, YAP-dependent transcription factors, protein stability, βTrCP |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124717314493 |
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