Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California at Berkeley, Berkeley, California, United States of America.
PLoS One. 2010 Feb 16;5(2):e9229. doi: 10.1371/journal.pone.0009229.
FoxM1 is a forkhead box transcription factor and a known master regulator required for different phases of the cell cycle. In cell lines, FoxM1 deficient cells exhibit delayed S phase entry, aneuploidy, polyploidy and can't complete mitosis. In vivo, FoxM1 is expressed mostly in proliferating cells but is surprisingly also found in non-proliferating CD4(+)CD8(+) double positive thymocytes. Here, we addressed the role of FoxM1 in T cell development by generating and analyzing two different lines of T-cell specific FoxM1 deficient mice. As expected, FoxM1 is required for proliferation of early thymocytes and activated mature T cells. Defective expression of many cell cycle proteins was detected, including cyclin A, cyclin B1, cdc2, cdk2, p27 and the Rb family members p107 and p130 but surprisingly not survivin. Unexpectedly, loss of FoxM1 only affects a few cell cycle proteins in CD4(+)CD8(+) thymocytes and has little effect on their sensitivity to apoptosis and the subsequent steps of T cell differentiation. Thus, regulation of cell cycle genes by FoxM1 is stage- and context-dependent.
FoxM1 是一种叉头框转录因子，是细胞周期不同阶段所必需的已知主调控因子。在细胞系中，FoxM1 缺陷细胞表现出 S 期进入延迟、非整倍体、多倍体，并且不能完成有丝分裂。在体内，FoxM1 主要在增殖细胞中表达，但令人惊讶的是，它也存在于非增殖的 CD4(+)CD8(+)双阳性胸腺细胞中。在这里，我们通过生成和分析两种不同的 T 细胞特异性 FoxM1 缺陷小鼠来研究 FoxM1 在 T 细胞发育中的作用。正如预期的那样，FoxM1 是早期胸腺细胞和激活的成熟 T 细胞增殖所必需的。检测到许多细胞周期蛋白的表达缺陷，包括细胞周期蛋白 A、细胞周期蛋白 B1、CDC2、CDK2、p27 和 Rb 家族成员 p107 和 p130，但令人惊讶的是，survivin 不受影响。出乎意料的是，FoxM1 的缺失仅影响 CD4(+)CD8(+)胸腺细胞中的少数细胞周期蛋白，对其对细胞凋亡的敏感性及其随后的 T 细胞分化步骤影响很小。因此，FoxM1 对细胞周期基因的调节是阶段和上下文依赖的。
