E2F1: Cause and Consequence of DNA Replication Stress.
E2F1: Cause and Consequence of DNA Replication Stress.
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DOI：
10.3389/fmolb.2020.599332
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发表时间：
2020
影响因子：
5
通讯作者：
D'Angiolella V
中科院分区：
文献类型：
--
作者：
Fouad S;Hauton D;D'Angiolella V
在哺乳动物细胞中，细胞周期进入响应于正确的刺激而发生，并且由E2F家族成员的转录活性促进。E2F蛋白调节S期细胞周期蛋白和DNA复制、DNA修复和凋亡所需基因的转录。E2F1是E2F家族成员中最典型和研究最多的成员，其活性受到DNA损伤检查点的严格控制，以调节细胞周期进程并在需要时启动程序性细胞死亡。改变的肿瘤抑制和致癌信号通路通常导致直接或间接干扰E2F1调节，以确保独立于外部线索的更高细胞增殖率。尽管E2F1活性失调和癌症进展之间存在明确的联系，但关于E2F1对DNA复制应激表型的贡献的文献有些缺乏。这篇综述讨论了功能失调的肿瘤抑制和致癌信号通路如何促进E2F1转录的破坏，从而破坏其转录靶点，以及这些事件如何有可能驱动DNA复制应激。除了参与的E2F1上游的DNA复制应力，这份手稿还考虑了E2F1的作用，作为一个下游效应器的反应，这种类型的细胞应激。最后，综述介绍了E2F1活性如何通过翻译后调节与检查点控制相结合的一些思考，并提出了基于此轴的可利用的肿瘤弱点。
In mammalian cells, cell cycle entry occurs in response to the correct stimuli and is promoted by the transcriptional activity of E2F family members. E2F proteins regulate the transcription of S phase cyclins and genes required for DNA replication, DNA repair, and apoptosis. The activity of E2F1, the archetypal and most heavily studied E2F family member, is tightly controlled by the DNA damage checkpoints to modulate cell cycle progression and initiate programmed cell death, when required. Altered tumor suppressor and oncogenic signaling pathways often result in direct or indirect interference with E2F1 regulation to ensure higher rates of cell proliferation independently of external cues. Despite a clear link between dysregulated E2F1 activity and cancer progression, literature on the contribution of E2F1 to DNA replication stress phenotypes is somewhat scarce. This review discusses how dysfunctional tumor suppressor and oncogenic signaling pathways promote the disruption of E2F1 transcription and hence of its transcriptional targets, and how such events have the potential to drive DNA replication stress. In addition to the involvement of E2F1 upstream of DNA replication stress, this manuscript also considers the role of E2F1 as a downstream effector of the response to this type of cellular stress. Lastly, the review introduces some reflections on how E2F1 activity is integrated with checkpoint control through post-translational regulation, and proposes an exploitable tumor weakness based on this axis.
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影响因子：
64.8
作者：
Bartkova, J;Horejsi, Z;Bartek, J
通讯作者：
Bartek, J
DOI：
10.1038/nrm3255
发表时间：
2011-12-22
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.6
作者：
BROWN, NC;REICHARD, P
通讯作者：
REICHARD, P
影响因子：
4.8
作者：
Chabes, AL;Björklund, S;Thelander, L
通讯作者：
Thelander, L
影响因子：
12.4
作者：
D'Angiolella V;Guardavaccaro D
通讯作者：
Guardavaccaro D