Bilican Bilada, Goding Colin R
Signalling and Development Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey, RH8 0TL, UK.
Exp Cell Res. 2006 Jul 15;312(12):2358-66. doi: 10.1016/j.yexcr.2006.03.033. Epub 2006 May 6.
T-box transcription factors play key roles in development and in particular the determination or maintenance of cell fate. Tbx2 is a transcriptional repressor implicated in several developmental processes and which has also been implicated in cancer through its ability to suppress senescence via repression of the p19(ARF) and p21(Cip1) (CDKN1A) promoters. However, despite its importance, little is known about how Tbx2 may be regulated. Here, we show that Tbx2 protein expression is tightly regulated during cell cycle progression, with levels being low in G1, increasing in mid-S-phase and persisting at high levels though G2 until finally undergoing a dramatic reduction at the onset of mitosis. Moreover, in S-phase, Tbx2 is present at a subset of late, but not early, replication foci and a significant fraction of Tbx2 is tightly associated with the nucleus in small DNA-associated foci that do not correspond with telomeres, PML or cajal bodies. The results are consistent with Tbx2 playing a role in cell cycle progression and organization of subnuclear compartments.
T 盒转录因子在发育过程中发挥关键作用，尤其是在细胞命运的决定或维持方面。Tbx2 是一种转录抑制因子，参与多个发育过程，并且通过抑制 p19(ARF) 和 p21(Cip1)（CDKN1A）启动子来抑制衰老，从而也与癌症有关。然而，尽管其很重要，但关于 Tbx2 如何被调控却知之甚少。在这里，我们表明 Tbx2 蛋白表达在细胞周期进程中受到严格调控，其水平在 G1 期较低，在 S 期中期升高，并在 G2 期一直保持高水平，直到在有丝分裂开始时急剧下降。此外，在 S 期，Tbx2 存在于一部分晚期而非早期复制位点，并且相当一部分 Tbx2 紧密结合在与端粒、PML 或 Cajal 体不对应的小 DNA 相关核内小体中的细胞核上。这些结果与 Tbx2 在细胞周期进程和核内亚结构的组织中发挥作用一致。
