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Control of contact-inhibition by 4E-BP1 upregulation.

机译:通过4E-BP1上调控制接触抑制。

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摘要

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.
机译:尽管接触抑制是多细胞生物的基本过程,但如何在高细胞密度下抑制增殖仍知之甚少。在这里,我们显示了4E-BP1,一种主要的帽依赖性翻译阻遏物,在密度介导的细胞周期停滞中起关键作用。随着细胞达到汇合,4E-BP1启动子被激活并且4E-BP1蛋白量增加。相反,在4E-BP1沉默后,观察到的细胞增殖密度依赖性抑制作用明显降低。我们进一步表明,在高密度下,通过细胞周期的G(1)相的进程更快,并且在不同的细胞类型(其中4E-BP1被下调(稳定的shRNA表达或瞬时siRNA转染)或移除(删除)。因此,4E-BP1似乎是接触抑制的重要介体。

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