Ten‐Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy
ABSTRACT Ten‐eleven translocation (TET) family proteins are Fe(II)‐ and α‐ketoglutarate‐dependent dioxygenases, comprising three family members: TET1, TET2, and TET3. These enzymes drive DNA demethylation by sequentially oxidizing 5‐methylcytosine to 5‐hydroxymethylcytosine, 5‐formylcytosine, and 5‐...
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2025-07-01
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| Online Access: | https://doi.org/10.1002/mco2.70245 |
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| author | Junzhi Liang Xinni Na Lingbo Meng Lixia He Ting Shu Yuanyuan Fang Bowen Zhang Zhongyu Zhao Cuishan Guo Tingting Li Zhijing Na Da Li Xue Xiao |
| author_facet | Junzhi Liang Xinni Na Lingbo Meng Lixia He Ting Shu Yuanyuan Fang Bowen Zhang Zhongyu Zhao Cuishan Guo Tingting Li Zhijing Na Da Li Xue Xiao |
| author_sort | Junzhi Liang |
| collection | DOAJ |
| description | ABSTRACT Ten‐eleven translocation (TET) family proteins are Fe(II)‐ and α‐ketoglutarate‐dependent dioxygenases, comprising three family members: TET1, TET2, and TET3. These enzymes drive DNA demethylation by sequentially oxidizing 5‐methylcytosine to 5‐hydroxymethylcytosine, 5‐formylcytosine, and 5‐carboxylcytosine. Through these reactions, TET proteins remodel the epigenetic landscape and interact with transcription factors and RNA polymerase II to regulate gene expression, cell lineage specification, and embryonic development. Mutations and dysregulation of TETs have been associated with the pathogenesis of various diseases, including the nervous system, immune system, and metabolic diseases, as well as cancers. Therapeutic modulation of TETs may be an effective strategy for the treatment of these diseases. Here, we provide a comprehensive overview of the mechanisms by which TET proteins mediate DNA demethylation and detail their biological functions. Additionally, we highlight recent advances in understanding the molecular mechanisms linking TET dysregulation to disease pathogenesis and explore their potential as therapeutic targets. This review supplements the current understanding of the critical role of epigenetic regulation in disease pathogenesis and further facilitates the rational design of targeted therapeutic agents for diseases associated with mutations and dysregulation of TETs. |
| format | Article |
| id | doaj-art-b9dc3295e74545dca7e9c6fcdbbac71e |
| institution | DOAJ |
| issn | 2688-2663 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-b9dc3295e74545dca7e9c6fcdbbac71e2025-08-20T02:39:24ZengWileyMedComm2688-26632025-07-0167n/an/a10.1002/mco2.70245Ten‐Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted TherapyJunzhi Liang0Xinni Na1Lingbo Meng2Lixia He3Ting Shu4Yuanyuan Fang5Bowen Zhang6Zhongyu Zhao7Cuishan Guo8Tingting Li9Zhijing Na10Da Li11Xue Xiao12Center of Reproductive Medicine Department of Obstetrics and Gynecology Shengjing Hospital of China Medical University Shenyang ChinaDepartment of Obstetrics and Gynecology Shengjing Hospital of China Medical University Shenyang ChinaCenter of Reproductive Medicine Department of Obstetrics and Gynecology Shengjing Hospital of China Medical University Shenyang ChinaCenter of Reproductive Medicine Department of Obstetrics and Gynecology Shengjing Hospital of China Medical University Shenyang ChinaDepartment of Healthcare IT National Health Commission of the People's Republic of China National Institute of Hospital Administration Beijing ChinaCenter of Reproductive Medicine Department of Obstetrics and Gynecology Shengjing Hospital of China Medical University Shenyang ChinaCenter of Reproductive Medicine Department of Obstetrics and Gynecology Shengjing Hospital of China Medical University Shenyang ChinaCenter of Reproductive Medicine Department of Obstetrics and Gynecology Shengjing Hospital of China Medical University Shenyang ChinaDepartment of Obstetrics and Gynecology Shengjing Hospital of China Medical University Shenyang ChinaDepartment of General Internal Medicine VIP Ward Liaoning Cancer Hospital & Institute Shenyang ChinaCenter of Reproductive Medicine Department of Obstetrics and Gynecology Shengjing Hospital of China Medical University Shenyang ChinaCenter of Reproductive Medicine Department of Obstetrics and Gynecology Shengjing Hospital of China Medical University Shenyang ChinaDepartment of Gynecology and Obstetrics West China Second University Hospital Sichuan University Chengdu ChinaABSTRACT Ten‐eleven translocation (TET) family proteins are Fe(II)‐ and α‐ketoglutarate‐dependent dioxygenases, comprising three family members: TET1, TET2, and TET3. These enzymes drive DNA demethylation by sequentially oxidizing 5‐methylcytosine to 5‐hydroxymethylcytosine, 5‐formylcytosine, and 5‐carboxylcytosine. Through these reactions, TET proteins remodel the epigenetic landscape and interact with transcription factors and RNA polymerase II to regulate gene expression, cell lineage specification, and embryonic development. Mutations and dysregulation of TETs have been associated with the pathogenesis of various diseases, including the nervous system, immune system, and metabolic diseases, as well as cancers. Therapeutic modulation of TETs may be an effective strategy for the treatment of these diseases. Here, we provide a comprehensive overview of the mechanisms by which TET proteins mediate DNA demethylation and detail their biological functions. Additionally, we highlight recent advances in understanding the molecular mechanisms linking TET dysregulation to disease pathogenesis and explore their potential as therapeutic targets. This review supplements the current understanding of the critical role of epigenetic regulation in disease pathogenesis and further facilitates the rational design of targeted therapeutic agents for diseases associated with mutations and dysregulation of TETs.https://doi.org/10.1002/mco2.70245Biological functionsDemethylationDiseasesTen‐eleven translocationTherapeutic strategies |
| spellingShingle | Junzhi Liang Xinni Na Lingbo Meng Lixia He Ting Shu Yuanyuan Fang Bowen Zhang Zhongyu Zhao Cuishan Guo Tingting Li Zhijing Na Da Li Xue Xiao Ten‐Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy MedComm Biological functions Demethylation Diseases Ten‐eleven translocation Therapeutic strategies |
| title | Ten‐Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy |
| title_full | Ten‐Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy |
| title_fullStr | Ten‐Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy |
| title_full_unstemmed | Ten‐Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy |
| title_short | Ten‐Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy |
| title_sort | ten eleven translocation family proteins structure biological functions diseases and targeted therapy |
| topic | Biological functions Demethylation Diseases Ten‐eleven translocation Therapeutic strategies |
| url | https://doi.org/10.1002/mco2.70245 |
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