Journal
JOURNAL OF AUTOIMMUNITY
Volume 96, Issue -, Pages 74-85Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2018.08.006
Keywords
CRL4(DCAF2); Cell cycle; Aurora B; Proteasome activity; H4K20me1
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Funding
- National Key Research and Development Program of China [2018YFD0500100]
- National Natural Science Foundation of China [81572651/81771675]
- Fundamental Research Funds for the Central Universities [2016QN81013]
- Thousand Young Talents Plan of China
- Zhejiang University Special Fund for Fundamental Research
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The proliferation of T cells in peripheral lymphoid tissues requires T cell receptor (TCR)-mediated cell cycle entry. However, the underlying mechanism regulating cell cycle progression in mature T cells is incompletely understood. Here, we have identified an E3 ubiquitin ligase, CRL4(DCAF2), as a critical mediator controlling M phase exit in activated T cells. DCAF2 expression is induced upon TCR stimulation and its deficiency attenuates T cell expansion. Additionally, DCAF2 T cell-specific knockout mice display impaired peripheral T cell maintenance and reduced severity of various autoimmune diseases. Continuous H4K20me1 modification caused by DCAF2 deficiency inhibits the induction of Aurkb expression, which regulates 26S proteasome activity during G2/M phase. CRL4(DCAF2) deficiency causes M phase arrest through proteasome-dependent mechanisms in peripheral T cells. Our findings establish DCAF2 as a novel target for T cell-mediated autoimmunity or inflammatory diseases.
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