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首页> 外文期刊>Molecular and Cellular Biology >Hes1 Directly Controls Cell Proliferation through the Transcriptional Repression of p27Kip1
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Hes1 Directly Controls Cell Proliferation through the Transcriptional Repression of p27Kip1

机译：HES1通过P27KIP1的转录抑制直接控制细胞增殖

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A transcriptional regulator, Hes1, plays crucial roles in the control of differentiation and proliferation of neuronal, endocrine, and T-lymphocyte progenitors during development. Mechanisms for the regulation of cell proliferation by Hes1, however, remain to be verified. In embryonic carcinoma cells, endogenous Hes1 expression was repressed by retinoic acid in concord with enhanced p27Kip1 expression and cell cycle arrest. Conversely, conditional expression of a moderate but not maximal level of Hes1 in HeLa cells by a tetracycline-inducible system resulted in reduced p27Kip1 expression, which was attributed to decreased basal transcript rather than enhanced proteasomal degradation, with concomitant increases in the growth rate and saturation density. Hes1 induction repressed the promoter activity of a 5′ flanking basal enhancer region of p27Kip1 gene in a manner dependent on Hes1 expression levels, and this was mediated by its binding to class C sites in the promoter region. Finally, hypoplastic fetal thymi, as well as livers and brains of Hes1-deficient mice, showed significantly increased p27Kip1 transcripts compared with those of control littermates. These results have suggested that Hes1 directly contributes to the promotion of progenitor cell proliferation through transcriptional repression of a cyclin-dependent kinase inhibitor, p27Kip1.
机译：转录调节剂HES1在发育过程中控制神经元，内分泌和T淋巴细胞祖细胞祖细胞祖细胞分化和增殖中的关键作用。然而，HES1对细胞增殖调节的机制仍然核实。在胚胎癌细胞中，通过增强的P27 Kip1 表达和细胞循环捕获，通过在官方酸中抑制内源性HES1表达。相反，通过四环素诱导系统的HELA细胞中温和但不是最大程度的HES1的条件表达导致P27 KIP1 表达还原，其归因于增加基础转录物而不是增强的蛋白酶体降解伴随的增长率和饱和密度增加。 HES1以依赖于HES1表达水平的方式抑制p27 Kip1-/ sup>基因的5'侧翼基础增强区的启动子活性，并且这通过其与启动子区域中的C类网站的结合介导。最后，与对照凋落物相比，HESE1 HES1 -Defige小鼠的复杂胎儿胸腺，以及 HES1 -Defigle小鼠的肝脏和大脑显示显着增加。这些结果表明，HES1直接有助于通过基蛋白依赖性激酶抑制剂的转录抑制抑制祖细胞增殖，P27 Kip1 。

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