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

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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.

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Acknowledgements

We thank Bullet Edits Limited for the linguistic editing and proofreading of the manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (32170975), Suzhou Science and Technology Project (SKY2022115), Scientific Research Project of Wuxi Municipal Health Commission (Q202201), and the Social Development-Science & Technology Demonstration Projects of Wuxi (N20201005).

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  1. Ruirong Wu and Xiufeng Wu have contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi, 214028, Jiangsu, China

    Ruirong Wu & Yong Mao

  2. Department of Pharmacy, Affiliated Hospital of Jiangnan University, Wuxi, 214028, Jiangsu, China

    Xiufeng Wu

  3. Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, 199 Renai Road, Suzhou, 215123, Jiangsu, China

    Lu Zou & Liang Zhou

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  1. Ruirong Wu
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RW, XW, and LZ performed the experiments. LZ and YM supervised this research. LZ and YM wrote and revised the manuscript.

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Correspondence to Liang Zhou or Yong Mao.

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Wu, R., Wu, X., Zou, L. et al. DDB1 regulates the activation-induced apoptosis of T cells via downregulating the expression of histone methyltransferase SETD7. Med Oncol 40, 146 (2023). https://doi.org/10.1007/s12032-023-02015-8

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