Decrotonylation of AKT1 promotes AKT1 phosphorylation and activation during myogenic differentiation
Introduction: Myogenic differentiation plays an important role in pathophysiological processes including muscle injury and regeneration, as well as muscle atrophy. A novel type of posttranslational modification, crotonylation, has been reported to play a role in stem cell differentiation and disease...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Journal of Advanced Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123222002351 |
| _version_ | 1797769797639864320 |
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| author | Zhengyu Qian Jingwei Ye Jinteng Li Yunshu Che Wenhui Yu Peitao Xu Jiajie Lin Feng Ye Xiaojun Xu Zepeng Su Dateng Li Zhongyu Xie Yanfeng Wu Huiyong Shen |
| author_facet | Zhengyu Qian Jingwei Ye Jinteng Li Yunshu Che Wenhui Yu Peitao Xu Jiajie Lin Feng Ye Xiaojun Xu Zepeng Su Dateng Li Zhongyu Xie Yanfeng Wu Huiyong Shen |
| author_sort | Zhengyu Qian |
| collection | DOAJ |
| description | Introduction: Myogenic differentiation plays an important role in pathophysiological processes including muscle injury and regeneration, as well as muscle atrophy. A novel type of posttranslational modification, crotonylation, has been reported to play a role in stem cell differentiation and disease. However, the role of crotonylation in myogenic differentiation has not been clarified. Objectives: This study aims to find the role of crotonylation during myogenic differentiation and explore whether it is a potential target in myogenic dysfunction disease. Methods: C2C12 cell line and skeletal muscle mesenchymal progenitors of Mus musculus were used for myogenic process study in vitro, while muscle injury model of mice was used for in vivo muscle regeneration study. Mass spectrometry favored in discovery of potential target protein of crotonylation and its specific sites. Results: We confirmed the gradual decrease in total protein crotonylation level during muscle differentiation and found decreased crotonylation of AKT1, which facilitated an increase in AKT1 phosphorylation. Then we verified that crotonylation of AKT1 at specific sites weakened its binding with PDK1 and impaired its phosphorylation. In addition, we found that increased expression of the crotonylation eraser HDAC3 decreased AKT1 crotonylation levels during myogenic differentiation, jointly promoting myogenic differentiation. Conclusion: Our study highlights the important role of decrotonylation of AKT1 in the process of muscle differentiation, where it aids the phosphorylation and activation of AKT1 and promotes myogenic differentiation. This is of great significance for exploring the pathophysiological process of muscle injury repair and sarcopenia. |
| first_indexed | 2024-03-12T21:14:11Z |
| format | Article |
| id | doaj.art-b20827d5d71f4a46b39526268d9397aa |
| institution | Directory Open Access Journal |
| issn | 2090-1232 |
| language | English |
| last_indexed | 2024-03-12T21:14:11Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Advanced Research |
| spelling | doaj.art-b20827d5d71f4a46b39526268d9397aa2023-07-30T04:22:13ZengElsevierJournal of Advanced Research2090-12322023-08-0150117133Decrotonylation of AKT1 promotes AKT1 phosphorylation and activation during myogenic differentiationZhengyu Qian0Jingwei Ye1Jinteng Li2Yunshu Che3Wenhui Yu4Peitao Xu5Jiajie Lin6Feng Ye7Xiaojun Xu8Zepeng Su9Dateng Li10Zhongyu Xie11Yanfeng Wu12Huiyong Shen13Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, PR ChinaDepartment of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, PR ChinaDepartment of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, PR ChinaDepartment of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, PR ChinaDepartment of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, PR ChinaDepartment of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, PR ChinaDepartment of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, PR ChinaDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, PR ChinaDepartment of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, PR ChinaDepartment of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, PR China121 Westmoreland, White Plains, NY 10606, USADepartment of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, PR China; Corresponding authors at: Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, PR China (Huiyong Shen).Center for Biotherapy, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, PR China; Corresponding authors at: Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, PR China (Huiyong Shen).Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, PR China; Department of Orthopedics, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, PR China; Corresponding authors at: Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, PR China (Huiyong Shen).Introduction: Myogenic differentiation plays an important role in pathophysiological processes including muscle injury and regeneration, as well as muscle atrophy. A novel type of posttranslational modification, crotonylation, has been reported to play a role in stem cell differentiation and disease. However, the role of crotonylation in myogenic differentiation has not been clarified. Objectives: This study aims to find the role of crotonylation during myogenic differentiation and explore whether it is a potential target in myogenic dysfunction disease. Methods: C2C12 cell line and skeletal muscle mesenchymal progenitors of Mus musculus were used for myogenic process study in vitro, while muscle injury model of mice was used for in vivo muscle regeneration study. Mass spectrometry favored in discovery of potential target protein of crotonylation and its specific sites. Results: We confirmed the gradual decrease in total protein crotonylation level during muscle differentiation and found decreased crotonylation of AKT1, which facilitated an increase in AKT1 phosphorylation. Then we verified that crotonylation of AKT1 at specific sites weakened its binding with PDK1 and impaired its phosphorylation. In addition, we found that increased expression of the crotonylation eraser HDAC3 decreased AKT1 crotonylation levels during myogenic differentiation, jointly promoting myogenic differentiation. Conclusion: Our study highlights the important role of decrotonylation of AKT1 in the process of muscle differentiation, where it aids the phosphorylation and activation of AKT1 and promotes myogenic differentiation. This is of great significance for exploring the pathophysiological process of muscle injury repair and sarcopenia.http://www.sciencedirect.com/science/article/pii/S2090123222002351CrotonylationPhosphorylationMyogenic differentiationAKT1 |
| spellingShingle | Zhengyu Qian Jingwei Ye Jinteng Li Yunshu Che Wenhui Yu Peitao Xu Jiajie Lin Feng Ye Xiaojun Xu Zepeng Su Dateng Li Zhongyu Xie Yanfeng Wu Huiyong Shen Decrotonylation of AKT1 promotes AKT1 phosphorylation and activation during myogenic differentiation Journal of Advanced Research Crotonylation Phosphorylation Myogenic differentiation AKT1 |
| title | Decrotonylation of AKT1 promotes AKT1 phosphorylation and activation during myogenic differentiation |
| title_full | Decrotonylation of AKT1 promotes AKT1 phosphorylation and activation during myogenic differentiation |
| title_fullStr | Decrotonylation of AKT1 promotes AKT1 phosphorylation and activation during myogenic differentiation |
| title_full_unstemmed | Decrotonylation of AKT1 promotes AKT1 phosphorylation and activation during myogenic differentiation |
| title_short | Decrotonylation of AKT1 promotes AKT1 phosphorylation and activation during myogenic differentiation |
| title_sort | decrotonylation of akt1 promotes akt1 phosphorylation and activation during myogenic differentiation |
| topic | Crotonylation Phosphorylation Myogenic differentiation AKT1 |
| url | http://www.sciencedirect.com/science/article/pii/S2090123222002351 |
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