SUMOylation of TEAD1 Modulates the Mechanism of Pathological Cardiac Hypertrophy
Abstract Pathological cardiac hypertrophy is the leading cause of heart failure and has an extremely complicated pathogenesis. TEA domain transcription factor 1 (TEAD1) is recognized as an important transcription factor that plays a key regulatory role in cardiovascular disease. This study aimed to...
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| Format: | Article |
| Language: | English |
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Wiley
2024-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202305677 |
| _version_ | 1797242674483298304 |
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| author | Xin Shi Xuening Dang Zhenyu Huang Yanqiao Lu Huan Tong Feng Liang Fei Zhuang Yi Li Zhaohua Cai Huanhuan Huo Zhaolei Jiang Changqing Pan Xia Wang Chang Gu Ben He |
| author_facet | Xin Shi Xuening Dang Zhenyu Huang Yanqiao Lu Huan Tong Feng Liang Fei Zhuang Yi Li Zhaohua Cai Huanhuan Huo Zhaolei Jiang Changqing Pan Xia Wang Chang Gu Ben He |
| author_sort | Xin Shi |
| collection | DOAJ |
| description | Abstract Pathological cardiac hypertrophy is the leading cause of heart failure and has an extremely complicated pathogenesis. TEA domain transcription factor 1 (TEAD1) is recognized as an important transcription factor that plays a key regulatory role in cardiovascular disease. This study aimed to explore the role of TEAD1 in cardiac hypertrophy and to clarify the regulatory role of small ubiquitin‐like modifier (SUMO)‐mediated modifications. First, the expression level of TEAD1 in patients with heart failure, mice, and cardiomyocytes is investigated. It is discovered that TEAD1 is modified by SUMO1 during cardiac hypertrophy and that the process of deSUMOylation is regulated by SUMO‐specific protease 1 (SENP1). Lysine 173 is an essential site for TEAD1 SUMOylation, which affects the protein stability, nuclear localization, and DNA‐binding ability of TEAD1 and enhances the interaction between TEAD1 and its transcriptional co‐activator yes‐associated protein 1 in the Hippo pathway. Finally, adeno‐associated virus serotype 9 is used to construct TEAD1 wild‐type and KR mutant mice and demonstrated that the deSUMOylation of TEAD1 markedly exacerbated cardiomyocyte enlargement in vitro and in a mouse model of cardiac hypertrophy. The results provide novel evidence that the SUMOylation of TEAD1 is a promising therapeutic strategy for hypertrophy‐related heart failure. |
| first_indexed | 2024-04-24T18:42:58Z |
| format | Article |
| id | doaj.art-25f11daacce947a7b90b8c8488e2c04d |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-24T18:42:58Z |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-25f11daacce947a7b90b8c8488e2c04d2024-03-27T09:39:52ZengWileyAdvanced Science2198-38442024-03-011112n/an/a10.1002/advs.202305677SUMOylation of TEAD1 Modulates the Mechanism of Pathological Cardiac HypertrophyXin Shi0Xuening Dang1Zhenyu Huang2Yanqiao Lu3Huan Tong4Feng Liang5Fei Zhuang6Yi Li7Zhaohua Cai8Huanhuan Huo9Zhaolei Jiang10Changqing Pan11Xia Wang12Chang Gu13Ben He14Department of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiovascular Surgery Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Central Laboratory Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiothoracic Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaGeneral Surgery Department Shanghai Chest Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiothoracic Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaAbstract Pathological cardiac hypertrophy is the leading cause of heart failure and has an extremely complicated pathogenesis. TEA domain transcription factor 1 (TEAD1) is recognized as an important transcription factor that plays a key regulatory role in cardiovascular disease. This study aimed to explore the role of TEAD1 in cardiac hypertrophy and to clarify the regulatory role of small ubiquitin‐like modifier (SUMO)‐mediated modifications. First, the expression level of TEAD1 in patients with heart failure, mice, and cardiomyocytes is investigated. It is discovered that TEAD1 is modified by SUMO1 during cardiac hypertrophy and that the process of deSUMOylation is regulated by SUMO‐specific protease 1 (SENP1). Lysine 173 is an essential site for TEAD1 SUMOylation, which affects the protein stability, nuclear localization, and DNA‐binding ability of TEAD1 and enhances the interaction between TEAD1 and its transcriptional co‐activator yes‐associated protein 1 in the Hippo pathway. Finally, adeno‐associated virus serotype 9 is used to construct TEAD1 wild‐type and KR mutant mice and demonstrated that the deSUMOylation of TEAD1 markedly exacerbated cardiomyocyte enlargement in vitro and in a mouse model of cardiac hypertrophy. The results provide novel evidence that the SUMOylation of TEAD1 is a promising therapeutic strategy for hypertrophy‐related heart failure.https://doi.org/10.1002/advs.202305677cardiac hypertrophyoxidative stresspost‐translational modificationSUMOylationTEA domain transcription factor 1 |
| spellingShingle | Xin Shi Xuening Dang Zhenyu Huang Yanqiao Lu Huan Tong Feng Liang Fei Zhuang Yi Li Zhaohua Cai Huanhuan Huo Zhaolei Jiang Changqing Pan Xia Wang Chang Gu Ben He SUMOylation of TEAD1 Modulates the Mechanism of Pathological Cardiac Hypertrophy Advanced Science cardiac hypertrophy oxidative stress post‐translational modification SUMOylation TEA domain transcription factor 1 |
| title | SUMOylation of TEAD1 Modulates the Mechanism of Pathological Cardiac Hypertrophy |
| title_full | SUMOylation of TEAD1 Modulates the Mechanism of Pathological Cardiac Hypertrophy |
| title_fullStr | SUMOylation of TEAD1 Modulates the Mechanism of Pathological Cardiac Hypertrophy |
| title_full_unstemmed | SUMOylation of TEAD1 Modulates the Mechanism of Pathological Cardiac Hypertrophy |
| title_short | SUMOylation of TEAD1 Modulates the Mechanism of Pathological Cardiac Hypertrophy |
| title_sort | sumoylation of tead1 modulates the mechanism of pathological cardiac hypertrophy |
| topic | cardiac hypertrophy oxidative stress post‐translational modification SUMOylation TEA domain transcription factor 1 |
| url | https://doi.org/10.1002/advs.202305677 |
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