DDB1 regulates the activation-induced apoptosis of T cells via downregulating the expression of histone methyltransferase SETD7

  • Med Oncol. 2023 Apr 12;40(5):146. doi: 10.1007/s12032-023-02015-8.
Ruirong Wu  #  1 Xiufeng Wu  #  2 Lu Zou  3 Liang Zhou  4 Yong Mao  5
Affiliations
  • 1. Department of Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi, 214028, Jiangsu, China.
  • 2. Department of Pharmacy, Affiliated Hospital of Jiangnan University, Wuxi, 214028, Jiangsu, China.
  • 3. Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, 199 Renai Road, Suzhou, 215123, Jiangsu, China.
  • 4. Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, 199 Renai Road, Suzhou, 215123, Jiangsu, China. [email protected].
  • 5. Department of Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi, 214028, Jiangsu, China. [email protected].
  • # Contributed equally.
Abstract

The damaged DNA-binding protein 1 (DDB1) enhances the survival and maintenance of multipotent cells through promoting the Cullin 4 E3 Ligase complex-dependent ubiquitination and subsequent degradation of downstream substrates. Naive T cells could be activated and differentiated into effector and memory T cells by exogenous stimulatory molecules, which are essential in immune response and inflammation. However, possible regulation and molecular mechanisms of DDB1 in T-cell activation-induced Apoptosis were largely unknown. Here, in this study, we uncovered that DDB1 could downregulate the expression of Histone Methyltransferase SETD7 through decreasing its mRNA level and then regulated activation-induced Apoptosis of T-cell line Jurkat cells. Furthermore, RNA-sequencing assay on activated Jurkat cells confirmed that the SETD7 attenuated the activation of Jurkat cells. Our study revealed the non-enzymatic functions of DDB1 on the activation-induced Apoptosis of T cells.

Keywords
Activation-induced apoptosis; DDB1; RNA sequencing; SETD7; T cells.
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