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DCAF1 controls T-cell function via p53-dependent and -independent mechanisms

Author

Listed:
  • Zengli Guo

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Qing Kong

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    Deparment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill)

  • Cui Liu

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    Deparment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill)

  • Song Zhang

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Liyun Zou

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Feng Yan

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    Deparment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill)

  • Jason K. Whitmire

    (University of North Carolina at Chapel Hill)

  • Yue Xiong

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    Deparment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill)

  • Xian Chen

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    Deparment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill)

  • Yisong Y. Wan

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College)

Abstract

On activation, naive T cells grow in size and enter cell cycle to mount immune response. How the fundamental processes of T-cell growth and cell cycle entry are regulated is poorly understood. Here we report that DCAF1 (Ddb1–cullin4-associated-factor 1) is essential for these processes. The deletion of DCAF1 in T cells impairs their peripheral homeostasis. DCAF1 is upregulated on T-cell receptor activation and critical for activation-induced T-cell growth, cell cycle entry and proliferation. In addition, DCAF1 is required for T-cell expansion and function during anti-viral and autoimmune responses in vivo. DCAF1 deletion leads to a drastic stabilization of p53 protein, which can be attributed to a requirement of DCAF1 for MDM2-mediated p53 poly-ubiquitination. Importantly, p53 deletion rescues the cell cycle entry defect but not the growth defect of DCAF1-deficient cells. Therefore, DCAF1 is vital for T-cell function through p53-dependent and -independent mechanisms.

Suggested Citation

  • Zengli Guo & Qing Kong & Cui Liu & Song Zhang & Liyun Zou & Feng Yan & Jason K. Whitmire & Yue Xiong & Xian Chen & Yisong Y. Wan, 2016. "DCAF1 controls T-cell function via p53-dependent and -independent mechanisms," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10307
    DOI: 10.1038/ncomms10307
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    Cited by:

    1. Jingjie Yi & Omid Tavana & Huan Li & Donglai Wang & Richard J. Baer & Wei Gu, 2023. "Targeting USP2 regulation of VPRBP-mediated degradation of p53 and PD-L1 for cancer therapy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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