Pedraza-Alva Gustavo, Koulnis Miroslav, Charland Colette, Thornton Tina, Clements James L, Schlissel Mark S, Rincón Mercedes
Department of Medicine/Immunobiology Program, University of Vermont, Burlington, VT 05405, USA.
EMBO J. 2006 Feb 22;25(4):763-73. doi: 10.1038/sj.emboj.7600972. Epub 2006 Feb 2.
Delay of cell cycle progression in response to double-strand DNA breaks (DSBs) is critical to allow time for DNA repair and prevent cellular transformation. Here, we show that the p38 mitogen-activated protein (MAP) kinase signaling pathway is activated in immature thymocytes along with TcRbeta gene V(D)J recombination. Active p38 MAP kinase promotes a G2/M cell cycle checkpoint through the phosphorylation and activation of p53 in these cells in vivo. Inactivation of p38 MAP kinase and p53 is required for DN3 thymocytes to exit the G2/M checkpoint, progress through mitosis and further differentiate. We propose that p38 MAP kinase is activated by V(D)J-mediated DSBs and induces a p53-mediated G2/M checkpoint to allow DNA repair and prevent cellular transformation.
响应双链DNA断裂（DSB）时细胞周期进程的延迟对于留出时间进行DNA修复和防止细胞转化至关重要。在此，我们表明p38丝裂原活化蛋白（MAP）激酶信号通路在未成熟胸腺细胞中随着TCRβ基因V（D）J重组而被激活。活性p38 MAP激酶通过体内这些细胞中p53的磷酸化和激活来促进G2/M细胞周期检查点。DN3胸腺细胞要退出G2/M检查点、经历有丝分裂并进一步分化，就需要使p38 MAP激酶和p53失活。我们提出p38 MAP激酶由V（D）J介导的DSB激活，并诱导p53介导的G2/M检查点以允许DNA修复并防止细胞转化。
