Mina53 catalyzes arginine demethylation of p53 to promote tumor growth
Summary: Arginine methylation is a common post-translational modification that plays critical roles in many biological processes. However, the existence of arginine demethylases that remove the modification has not been fully established. Here, we report that Myc-induced nuclear antigen 53 (Mina53),...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725000130 |
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| author | Lixiao Zhou Liyang Yu Shushu Song Yong Wang Qiang Zhu Meng Li Yutong Sha Liang Xu Xin Shu Qingqing Liao Ting Wu Bing Yang Siyuan Chai Bingyi Lin Liming Wu Ruhong Zhou Xiaotao Duan Chenggang Zhu Yuanyuan Ruan Wen Yi |
| author_facet | Lixiao Zhou Liyang Yu Shushu Song Yong Wang Qiang Zhu Meng Li Yutong Sha Liang Xu Xin Shu Qingqing Liao Ting Wu Bing Yang Siyuan Chai Bingyi Lin Liming Wu Ruhong Zhou Xiaotao Duan Chenggang Zhu Yuanyuan Ruan Wen Yi |
| author_sort | Lixiao Zhou |
| collection | DOAJ |
| description | Summary: Arginine methylation is a common post-translational modification that plays critical roles in many biological processes. However, the existence of arginine demethylases that remove the modification has not been fully established. Here, we report that Myc-induced nuclear antigen 53 (Mina53), a member of the jumonji C (JmjC) protein family, is an arginine demethylase. Mina53 catalyzes the removal of asymmetric dimethylation at arginine 337 of p53. Mina53-mediated demethylation reduces p53 stability and oligomerization and alters chromatin modifications at the gene promoter, thereby suppressing p53-mediated transcriptional activation and cell-cycle arrest. Mina53 represses p53-dependent tumor suppression both in mouse xenografts and spontaneous tumor models. Moreover, downregulation of p53-mediated gene expression is observed in several types of cancer with elevated expression of Mina53. Thus, our study reveals a regulatory mechanism of p53 homeostasis and activity and, more broadly, defines a paradigm for dynamic arginine methylation in controlling important biological functions. |
| format | Article |
| id | doaj-art-89f4d8d2fd9a4a6fa0df16262b3a19e9 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-89f4d8d2fd9a4a6fa0df16262b3a19e92025-01-27T04:21:53ZengElsevierCell Reports2211-12472025-02-01442115242Mina53 catalyzes arginine demethylation of p53 to promote tumor growthLixiao Zhou0Liyang Yu1Shushu Song2Yong Wang3Qiang Zhu4Meng Li5Yutong Sha6Liang Xu7Xin Shu8Qingqing Liao9Ting Wu10Bing Yang11Siyuan Chai12Bingyi Lin13Liming Wu14Ruhong Zhou15Xiaotao Duan16Chenggang Zhu17Yuanyuan Ruan18Wen Yi19Ministry of Education Key Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou, ChinaMinistry of Education Key Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou, ChinaNHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, ChinaMinistry of Education Key Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou, China; The Provincial International Science and Technology Cooperation Base on Engineering Biology, International Campus of Zhejiang University, Haining, ChinaMinistry of Education Key Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou, ChinaMinistry of Education Key Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou, ChinaMinistry of Education Key Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou, ChinaMinistry of Education Key Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou, ChinaLife Science Institute, Zhejiang University, Hangzhou, ChinaLife Science Institute, Zhejiang University, Hangzhou, ChinaLife Science Institute, Zhejiang University, Hangzhou, ChinaLife Science Institute, Zhejiang University, Hangzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang Provincial Key Laboratory of Pancreatic Disease, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang Provincial Key Laboratory of Pancreatic Disease, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang Provincial Key Laboratory of Pancreatic Disease, School of Medicine, Zhejiang University, Hangzhou, ChinaMinistry of Education Key Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou, China; The Provincial International Science and Technology Cooperation Base on Engineering Biology, International Campus of Zhejiang University, Haining, China; Cancer Center, Zhejiang University, Hangzhou, ChinaState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, ChinaMinistry of Education Key Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou, ChinaNHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China; Corresponding authorMinistry of Education Key Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang Provincial Key Laboratory of Pancreatic Disease, School of Medicine, Zhejiang University, Hangzhou, China; Cancer Center, Zhejiang University, Hangzhou, China; Corresponding authorSummary: Arginine methylation is a common post-translational modification that plays critical roles in many biological processes. However, the existence of arginine demethylases that remove the modification has not been fully established. Here, we report that Myc-induced nuclear antigen 53 (Mina53), a member of the jumonji C (JmjC) protein family, is an arginine demethylase. Mina53 catalyzes the removal of asymmetric dimethylation at arginine 337 of p53. Mina53-mediated demethylation reduces p53 stability and oligomerization and alters chromatin modifications at the gene promoter, thereby suppressing p53-mediated transcriptional activation and cell-cycle arrest. Mina53 represses p53-dependent tumor suppression both in mouse xenografts and spontaneous tumor models. Moreover, downregulation of p53-mediated gene expression is observed in several types of cancer with elevated expression of Mina53. Thus, our study reveals a regulatory mechanism of p53 homeostasis and activity and, more broadly, defines a paradigm for dynamic arginine methylation in controlling important biological functions.http://www.sciencedirect.com/science/article/pii/S2211124725000130CP: CancerCP: Molecular biology |
| spellingShingle | Lixiao Zhou Liyang Yu Shushu Song Yong Wang Qiang Zhu Meng Li Yutong Sha Liang Xu Xin Shu Qingqing Liao Ting Wu Bing Yang Siyuan Chai Bingyi Lin Liming Wu Ruhong Zhou Xiaotao Duan Chenggang Zhu Yuanyuan Ruan Wen Yi Mina53 catalyzes arginine demethylation of p53 to promote tumor growth Cell Reports CP: Cancer CP: Molecular biology |
| title | Mina53 catalyzes arginine demethylation of p53 to promote tumor growth |
| title_full | Mina53 catalyzes arginine demethylation of p53 to promote tumor growth |
| title_fullStr | Mina53 catalyzes arginine demethylation of p53 to promote tumor growth |
| title_full_unstemmed | Mina53 catalyzes arginine demethylation of p53 to promote tumor growth |
| title_short | Mina53 catalyzes arginine demethylation of p53 to promote tumor growth |
| title_sort | mina53 catalyzes arginine demethylation of p53 to promote tumor growth |
| topic | CP: Cancer CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725000130 |
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