Cyclin D/CDK4/6 activity controls G1 length in mammalian cells.

Cyclin D/CDK4/6 activity controls G1 length in mammalian cells.
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DOI:
10.1371/journal.pone.0185637
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Mathey-Prevot B
Mathey-Prevot B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Dong P;Zhang C;Parker BT;You L;Mathey-Prevot B

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细胞周期中G1期的长度在不同的细胞类型和组织类型中表现出显著的差异性。为了深入了解G1长度的控制,我们制作了一个E2F活性报告器,可以捕获Rb分离后的游离E2F活性,并实时跟踪其在单细胞水平上的激活动力学。我们的结果表明,它的活性与S相进展精确协调。定量分析表明,E2F转录动态和活性动态之间存在s期前的延迟。这种延迟在不同的细胞类型中是可变的,并通过Rb磷酸化受到细胞周期蛋白D/CDK4/6复合物活性的强烈调节。我们的研究结果表明,该复合物的主要功能是调节G1长度的适当时机。
The length of the G1 phase in the cell cycle shows significant variability in different cell types and tissue types. To gain insights into the control of G1 length, we generated an E2F activity reporter that captures free E2F activity after dissociation from Rb sequestration and followed its kinetics of activation at the single-cell level, in real time. Our results demonstrate that its activity is precisely coordinated with S phase progression. Quantitative analysis indicates that there is a pre-S phase delay between E2F transcriptional dynamic and activity dynamics. This delay is variable among different cell types and is strongly modulated by the cyclin D/CDK4/6 complex activity through Rb phosphorylation. Our findings suggest that the main function of this complex is to regulate the appropriate timing of G1 length.
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