2. Academic Validation
  3. Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy

Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy

  • MedComm (2020). 2025 Jul 1;6(7):e70245. doi: 10.1002/mco2.70245.
Junzhi Liang 1,  Xinni Na 2,  Lingbo Meng 1,  Lixia He 1,  Ting Shu 3,  Yuanyuan Fang 1,  Bowen Zhang 1,  Zhongyu Zhao 1,  Cuishan Guo 2,  Tingting Li 4,  Zhijing Na 1 5,  Da Li 1 5 6,  Xue Xiao 7 8
Affiliations

Affiliations

  • 1 Center of Reproductive Medicine Department of Obstetrics and Gynecology Shengjing Hospital of China Medical University Shenyang China.
  • 2 Department of Obstetrics and Gynecology Shengjing Hospital of China Medical University Shenyang China.
  • 3 Department of Healthcare IT National Health Commission of the People's Republic of China National Institute of Hospital Administration Beijing China.
  • 4 Department of General Internal Medicine VIP Ward Liaoning Cancer Hospital & Institute Shenyang China.
  • 5 NHC Key Laboratory of Advanced Reproductive Medicine and Fertility (China Medical University) National Health Commission Shenyang China.
  • 6 Key Laboratory of Reproductive Dysfunction Diseases and Fertility Remodeling of Liaoning Province Shenyang China.
  • 7 Department of Gynecology and Obstetrics West China Second University Hospital Sichuan University Chengdu China.
  • 8 Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) Ministry of Education, West China Second Hospital Sichuan University Chengdu China.
PMID: 40599235 DOI: 10.1002/mco2.70245
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.

Keywords

Biological functions; Demethylation; Diseases; Ten‐eleven translocation; Therapeutic strategies.

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