Hyper-SUMOylation of ERG Is Essential for the Progression of Acute Myeloid Leukemia
Leukemia is a malignant disease of hematopoietic tissue characterized by the differentiation arrest and malignant proliferation of immature hematopoietic precursor cells in bone marrow. ERG (ETS-related gene) is an important member of the E26 transformation-specific (ETS) transcription factor family...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.652284/full |
| _version_ | 1828897223711129600 |
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| author | Xu Chen Yuanyuan Qin Zhenzhen Zhang Zhengcao Xing Qiqi Wang Wenbin Lu Hong Yuan Congcong Du Xinyi Yang Yajie Shen Biying Zhao Huanjie Shao Xiaotong Wang Hongmei Wu Yitao Qi |
| author_facet | Xu Chen Yuanyuan Qin Zhenzhen Zhang Zhengcao Xing Qiqi Wang Wenbin Lu Hong Yuan Congcong Du Xinyi Yang Yajie Shen Biying Zhao Huanjie Shao Xiaotong Wang Hongmei Wu Yitao Qi |
| author_sort | Xu Chen |
| collection | DOAJ |
| description | Leukemia is a malignant disease of hematopoietic tissue characterized by the differentiation arrest and malignant proliferation of immature hematopoietic precursor cells in bone marrow. ERG (ETS-related gene) is an important member of the E26 transformation-specific (ETS) transcription factor family that plays a crucial role in physiological and pathological processes. However, the role of ERG and its modification in leukemia remains underexplored. In the present study, we stably knocked down or overexpressed ERG in leukemia cells and observed that ERG significantly promotes the proliferation and inhibits the differentiation of AML (acute myeloid leukemia) cells. Further experiments showed that ERG was primarily modified by SUMO2, which was deconjugated by SENP2. PML promotes the SUMOylation of ERG, enhancing its stability. Arsenic trioxide decreased the expression level of ERG, further promoting cell differentiation. Furthermore, the mutation of SUMO sites in ERG inhibited its ability to promote the proliferation and inhibit the differentiation of leukemia cells. Our results demonstrated the crucial role of ERG SUMOylation in the development of AML, providing powerful targeted therapeutic strategies for the clinical treatment of AML. |
| first_indexed | 2024-12-13T14:52:26Z |
| format | Article |
| id | doaj.art-42f296f7a8494b5b9e78d88f66bac8fa |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-13T14:52:26Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-42f296f7a8494b5b9e78d88f66bac8fa2022-12-21T23:41:18ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-03-01810.3389/fmolb.2021.652284652284Hyper-SUMOylation of ERG Is Essential for the Progression of Acute Myeloid LeukemiaXu Chen0Yuanyuan Qin1Zhenzhen Zhang2Zhengcao Xing3Qiqi Wang4Wenbin Lu5Hong Yuan6Congcong Du7Xinyi Yang8Yajie Shen9Biying Zhao10Huanjie Shao11Xiaotong Wang12Hongmei Wu13Yitao Qi14Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, ChinaKey Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, ChinaKey Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, ChinaKey Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, ChinaKey Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, ChinaKey Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, ChinaKey Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, ChinaKey Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, ChinaKey Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, ChinaKey Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, ChinaKey Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, ChinaKey Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, ChinaSchool of Agriculture, Ludong University, Yantai, ChinaKey Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, ChinaKey Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, ChinaLeukemia is a malignant disease of hematopoietic tissue characterized by the differentiation arrest and malignant proliferation of immature hematopoietic precursor cells in bone marrow. ERG (ETS-related gene) is an important member of the E26 transformation-specific (ETS) transcription factor family that plays a crucial role in physiological and pathological processes. However, the role of ERG and its modification in leukemia remains underexplored. In the present study, we stably knocked down or overexpressed ERG in leukemia cells and observed that ERG significantly promotes the proliferation and inhibits the differentiation of AML (acute myeloid leukemia) cells. Further experiments showed that ERG was primarily modified by SUMO2, which was deconjugated by SENP2. PML promotes the SUMOylation of ERG, enhancing its stability. Arsenic trioxide decreased the expression level of ERG, further promoting cell differentiation. Furthermore, the mutation of SUMO sites in ERG inhibited its ability to promote the proliferation and inhibit the differentiation of leukemia cells. Our results demonstrated the crucial role of ERG SUMOylation in the development of AML, providing powerful targeted therapeutic strategies for the clinical treatment of AML.https://www.frontiersin.org/articles/10.3389/fmolb.2021.652284/fullERGSUMO2SENP2PMLAML |
| spellingShingle | Xu Chen Yuanyuan Qin Zhenzhen Zhang Zhengcao Xing Qiqi Wang Wenbin Lu Hong Yuan Congcong Du Xinyi Yang Yajie Shen Biying Zhao Huanjie Shao Xiaotong Wang Hongmei Wu Yitao Qi Hyper-SUMOylation of ERG Is Essential for the Progression of Acute Myeloid Leukemia Frontiers in Molecular Biosciences ERG SUMO2 SENP2 PML AML |
| title | Hyper-SUMOylation of ERG Is Essential for the Progression of Acute Myeloid Leukemia |
| title_full | Hyper-SUMOylation of ERG Is Essential for the Progression of Acute Myeloid Leukemia |
| title_fullStr | Hyper-SUMOylation of ERG Is Essential for the Progression of Acute Myeloid Leukemia |
| title_full_unstemmed | Hyper-SUMOylation of ERG Is Essential for the Progression of Acute Myeloid Leukemia |
| title_short | Hyper-SUMOylation of ERG Is Essential for the Progression of Acute Myeloid Leukemia |
| title_sort | hyper sumoylation of erg is essential for the progression of acute myeloid leukemia |
| topic | ERG SUMO2 SENP2 PML AML |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.652284/full |
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