Song Jianxun, Salek-Ardakani Shahram, So Takanori, Croft Michael
Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
Nat Immunol. 2007 Jan;8(1):64-73. doi: 10.1038/ni1413. Epub 2006 Nov 26.
CD28-deficient T cells arrest at the G1-S transition of the cell cycle. Here we show that this is controlled by the kinase aurora B, which exists in a complex with survivin and mammalian target of rapamycin (mTOR). Expression of aurora B in Cd28-/- T cells augmented phosphorylation of mTOR substrates, expression of cyclin A, hyperphosphorylation of retinoblastoma protein and activation of cyclin-dependent kinases 1 and 2 and promoted cell cycle progression. Interleukin 2 enhanced aurora B activity, and inactive aurora B prevented interleukin 2-induced proliferation. Moreover, expression of aurora B restored Cd28-/- T cell proliferation and promoted inflammation in vivo. These data identify aurora B, along with survivin and mTOR, as a regulator of the G1-S checkpoint in T cells.
CD28缺陷型T细胞在细胞周期的G1-S转换阶段停滞。我们在此表明，这一过程由激酶极光激酶B控制，该激酶与生存素和雷帕霉素哺乳动物靶蛋白（mTOR）形成复合物存在。在Cd28-/- T细胞中极光激酶B的表达增强了mTOR底物的磷酸化、细胞周期蛋白A的表达、视网膜母细胞瘤蛋白的过度磷酸化以及细胞周期蛋白依赖性激酶1和2的激活，并促进了细胞周期进程。白细胞介素2增强了极光激酶B的活性，而失活的极光激酶B则阻止白细胞介素2诱导的增殖。此外，极光激酶B的表达恢复了Cd28-/- T细胞的增殖并促进了体内炎症。这些数据确定极光激酶B与生存素和mTOR一起，是T细胞中G1-S检查点的调节因子。
