CRL4DCAF2 is required for mature T-cell expansion via Aurora B-regulated proteasome activity.

CRL4DCAF2 is required for mature T-cell expansion via Aurora B-regulated proteasome activity. J Autoimmun. 2018 Sep 20;: Authors: Fan K, Wang F, Li Y, Chen L, Gao Z, Zhang Y, Duan JY, Huang T, Zhong J, Liu RB, Mao X, Fan H, Guo X, Jin J Abstract 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, CRL4DCAF2, 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. CRL4DCAF2 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. PMID: 30245026 [PubMed - as supplied by publisher]
Source: Journal of Autoimmunity - Category: Allergy & Immunology Authors: Tags: J Autoimmun Source Type: research