2. Academic Validation
  3. DCAF1 controls T-cell function via p53-dependent and -independent mechanisms

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

  • Nat Commun. 2016 Jan 5:7:10307. doi: 10.1038/ncomms10307.
Zengli Guo 1 2,  Qing Kong 1 2 3,  Cui Liu 1 3,  Song Zhang 1 2,  Liyun Zou 1 2,  Feng Yan 1 3,  Jason K Whitmire 4,  Yue Xiong 1 3,  Xian Chen 1 3,  Yisong Y Wan 1 2 5
Affiliations

Affiliations

  • 1 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
  • 2 Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
  • 3 Deparment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
  • 4 Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599 USA.
  • 5 Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China.
PMID: 26728942 DOI: 10.1038/ncomms10307
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.

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