Tet: novel anti-tumor drug target based on DNA demethylation / 上海交通大学学报（医学版）

ABSTRACT

Tet (ten-eleven translocation) proteins belong to α-ketoglutaric acid (α-KG or 2-OG) and Fe2+ dependent dioxygenases. Tets are found to be involved in the unique mammalian DNA active demethylation process by specifically oxidizing the methyl group of 5-methylcytosine (5mC) in mammalian genome, and play critical roles in gene regulation in early embryonic development and stem cell differentiation via regulating the dynamic balance distribution of 5mC. Abnormal expression and function of Tets are closely associated with various hematological malignances, including myelodysplastic syndrome, chronic myelomonocytic leukemia, and acute lymphoblastic leukemia, as well as solid tumors. Hence, Tets and Tets-mediated DNA demethylation are novel anti-tumor drug targets. Investigation of biological function and catalytic mechanism of Tets is helpful for further understanding mechanisms of tumor incidence and development relevant to DNA demethylation pathway and can provide reference for developing new anti-tumor targeted drugs.