| First Author | Fan K | Year | 2019 |
| Journal | J Autoimmun | Volume | 96 |
| Pages | 74-85 | PubMed ID | 30245026 |
| Mgi Jnum | J:294392 | Mgi Id | MGI:6456273 |
| Doi | 10.1016/j.jaut.2018.08.006 | Citation | Fan K, et al. (2019) CRL4(DCAF2) is required for mature T-cell expansion via Aurora B-regulated proteasome activity. J Autoimmun 96:74-85 |
| abstractText | 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. |
