Control of contact-inhibition by 4E-BP1 upregulation
Control of contact-inhibition by 4E-BP1 upregulation
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DOI：
10.4161/cc.9.7.11047
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发表时间：
2010-04-01
期刊：
影响因子：
4.3
通讯作者：
Pyronnet, Stephane
中科院分区：
文献类型：
--
作者：
Azar, Rania;Susini, Christiane;Pyronnet, Stephane
虽然接触抑制是多细胞生物体的基本过程，但在高细胞密度下如何抑制增殖仍然缺乏特征。在这里，我们表明，4 E-BP 1，帽依赖性翻译的一个主要阻遏物，在密度介导的细胞周期阻滞中起着关键作用。随着细胞达到汇合，4 E-BP 1启动子被激活并且4 E-BP 1蛋白量增加。相反，在4 E-BP 1沉默后观察到对细胞增殖的显著得多的密度依赖性抑制。我们进一步表明，在高密度下，通过细胞周期的G1期的进展更快，并且在不同的细胞类型中诱导细胞周期蛋白D1蛋白，其中4 E-BP 1已经下调（稳定的shRNA表达或瞬时siRNA转染）或去除（敲除）。因此，4 E-BP 1似乎是接触抑制的重要介质。
Although contact inhibition is a fundamental process for multicellular organisms, how proliferation is inhibited at high cellular densities remains poorly characterized. Here we show that 4E-BP1, one major repressor of cap-dependent translation, plays a critical role in density-mediated cell cycle arrest. 4E-BP1 promoter is activated and 4E-BP1 protein amount increases as cells reach confluence. Conversely, a much less marked density-dependent inhibition of cell proliferation is observed upon 4E-BP1 silencing. We further show that at high density, progression through the G 1 phase of the cell cycle is faster and Cyclin D1 protein is induced in different cell types where 4E-BP1 has been either downregulated (stable shRNA expression or transient siRNA transfection) or removed (knockout). Thus 4E-BP1 appears as an important mediator of contact inhibition.