CtBP-interacting BTB Zinc Finger Protein (CIBZ) Promotes Proliferation and G1/S Transition in Embryonic Stem Cells via Nanog
CtBP-interacting BTB Zinc Finger Protein (CIBZ) Promotes Proliferation and G1/S Transition in Embryonic Stem Cells via Nanog
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DOI：
10.1074/jbc.m111.333856
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发表时间：
2012-04-06
影响因子：
4.8
通讯作者：
Matsuda, Eishou
中科院分区：
文献类型：
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作者：
Nishii, Tomonori;Oikawa, Yu;Matsuda, Eishou
小鼠胚胎干细胞 (ESC) 需要转录调控以确保快速增殖，从而实现自我更新。然而，转录因子调节这种快速增殖的分子机制仍然很大程度上未知。在这里，我们提供的数据表明 CIBZ（一种 BTB 结构域锌指转录因子）是调节 ESC 增殖的关键转录调节因子。在这里，我们证明 CIBZ 的缺失或 siRNA 敲低会抑制 ESC 增殖。细胞周期分析表明，CIBZ 的缺失会延迟 ESC 从 G1 期向 S 期转变的进程。相反，外源 CIBZ 在 ESC 中的组成型异位表达可促进增殖并加速 G1/S 转变。这些发现表明，G1/S 转变的调节部分解释了 CIBZ 相关的 ESC 增殖。我们的数据表明，CIBZ 通过转录后调节 Nanog 的表达发挥作用，Nanog 是 ESC 增殖和 G1/S 转变的正调节因子，但不影响 Oct3/4 和 Sox2 蛋白的表达。值得注意的是，Nanog的组成型过表达部分挽救了CIBZ敲低引起的增殖缺陷，表明CIBZ在ESC增殖和G1/S转变中的作用至少部分取决于Nanog蛋白水平。
Mouse embryonic stem cells (ESCs) require transcriptional regulation to ensure rapid proliferation that allows for self-renewal. However, the molecular mechanism by which transcriptional factors regulate this rapid proliferation remains largely unknown. Here we present data showing that CIBZ, a BTB domain zinc finger transcriptional factor, is a key transcriptional regulator for regulation of ESC proliferation. Here we show that deletion or siRNA knockdown of CIBZ inhibits ESC proliferation. Cell cycle analysis shows that loss of CIBZ delays the progression of ESCs through the G1 to S phase transition. Conversely, constitutive ectopic expression of exogenous CIBZ in ESCs promotes proliferation and accelerates G1/S transition. These findings suggest that regulation of the G1/S transition explains, in part, CIBZ-associated ESC proliferation. Our data suggest that CIBZ acts through the post-transcriptionally regulates the expression of Nanog, a positive regulator of ESC proliferation and G1/S transition, but does not affect Oct3/4 and Sox2 protein expression. Notably, constitutive overexpression of Nanog partially rescued the proliferation defect caused by CIBZ knockdown, indicating the role of CIBZ in ESC proliferation and G1/S transition at least in part depends on the Nanog protein level.