Transcription factors LSF and E2Fs: tandem cyclists driving G0 to S?
Transcription factors LSF and E2Fs: tandem cyclists driving G0 to S?
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DOI：
10.4161/cc.8.14.9089
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发表时间：
2009-07-15
期刊：
影响因子：
--
通讯作者：
Saxena UH
中科院分区：
文献类型：
--
作者：
Hansen U;Owens L;Saxena UH
哺乳动物细胞的细胞周期进程从 G1 期进入 S 期需要感知和整合多个输入，以确定是否继续细胞 DNA 复制以及随后的细胞分裂。通向 S 需要通过限制点，该限制点在分子水平上由涉及 E2F 和 pRb 家族成员的双稳态开关组成。在 G1/S 边界，许多 DNA 复制和细胞周期进程必需的基因上调，促进进入 S 期。尽管激活 E2F 是驱动 G1/S 表达的最广泛表征的转录因子，但 LSF 也是刺激 G1/S 基因表达所必需的转录因子。此阶段的关键 LSF 靶基因 Tyms 编码胸苷酸合成酶。在研究 LSF 如何以细胞周期依赖性方式激活时，我们最近发现了一种新的时间延迟机制，用于在 G1 进展期间调节其活性，该机制显然独立于 E2F/pRb 轴。这涉及在 G1 早期通过两个主要的增殖信号通路抑制 LSF：ERK 和细胞周期蛋白 C/CDK，然后在 G1 中后期逐渐去磷酸化。 LSF 和 E2F 是否独立或协同作用以促进 G1/S 进展仍有待确定。
Cell cycle progression in mammalian cells from G1 into S phase requires sensing and integration of multiple inputs, in order to determine whether to continue to cellular DNA replication and subsequently, to cell division. Passage to S requires transition through the restriction point, which at a molecular level consists of a bistable switch involving E2Fs and pRb family members. At the G1/S boundary, a number of genes essential for DNA replication and cell cycle progression are upregulated, promoting entry into S phase. Although the activating E2Fs are the most extensively characterized transcription factors driving G1/S expression, LSF is also a transcription factor essential for stimulating G1/S gene expression. A critical LSF target gene at this stage, Tyms, encodes thymidylate synthetase. In investigating how LSF is activated in a cell cycle-dependent manner, we recently identified a novel time delay mechanism for regulating its activity during G1 progression, which is apparently independent of the E2F/pRb axis. This involves inhibition of LSF in early G1 by two major proliferative signaling pathways: ERK and cyclin C/CDK, followed by gradual dephosphorylation during mid- to late-G1. Whether LSF and E2F act independently or in concert to promote G1/S progression remains to be determined.
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影响因子：
64.5
作者：
Ren, SJ;Rollins, BJ
通讯作者：
Rollins, BJ
DOI：
10.1016/j.bbrc.2009.01.172
发表时间：
2009-03-20
影响因子：
3.1
作者：
Chae, Ji Hyung;Kang, Ho Chul;Kim, Chul Geun
通讯作者：
Kim, Chul Geun
DOI：
10.1073/pnas.84.17.6025
发表时间：
1987-09-01
影响因子：
11.1
作者：
KIM, CH;HEATH, C;HANSEN, U
通讯作者：
HANSEN, U
影响因子：
4.8
作者：
Ramamurthy, L;Barbour, V;Jane, SM
通讯作者：
Jane, SM
影响因子：
3.7
作者：
Conboy, Caitlin M.;Spyrou, Christiana;Thorne, Natalie P.;Wade, Elizabeth J.;Barbosa-Morais, Nuno L.;Wilson, Michael D.;Bhattacharjee, Arindam;Young, Richard A.;Tavare, Simon;Lees, Jacqueline A.;Odom, Duncan T.
通讯作者：
Odom, Duncan T.