Post-translational regulation of Oct4 transcriptional activity.
Post-translational regulation of Oct4 transcriptional activity.
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DOI：
10.1371/journal.pone.0004467
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Huang J
中科院分区：
文献类型：
--
作者：
Saxe JP;Tomilin A;Schöler HR;Plath K;Huang J
Oct4是调节胚胎干细胞增殖和分化的分子电路的关键组成部分。它对于维持未分化的多能细胞群是必不可少的，并通过以多个异二聚体和同二聚体构型结合DNA来完成这些任务。关于这些复合物的形成是如何调节的，或者Oct4蛋白对调节多能性的复杂细胞外刺激物的反应机制，人们知之甚少。在这里，我们提供的证据磷酸化为基础的机制，调节特定的Oct4同源二聚体构象。假定的磷酸化位点的点突变可以特异性地消除特定同源二聚体组装的转录活性，对其他构型几乎没有影响。此外，我们进行了生物信息学预测，以确定一个子集的Oct4靶基因，这可能是由这个特定的组件，并表明，改变Oct4蛋白水平影响Oct4靶基因的转录，这是由这个组件，而不是其他的调节。最后，我们确定了几种可能介导这种磷酸化的信号通路，并结合调节Oct4转录活性和蛋白质稳定性。这些结果提供了一种机制，快速和可逆的改变Oct4的反式激活潜力响应细胞外信号。
Oct4 is a key component of the molecular circuitry which regulates embryonic stem cell proliferation and differentiation. It is essential for maintenance of undifferentiated, pluripotent cell populations, and accomplishes these tasks by binding DNA in multiple heterodimer and homodimer configurations. Very little is known about how formation of these complexes is regulated, or the mechanisms through which Oct4 proteins respond to complex extracellular stimuli which regulate pluripotency. Here, we provide evidence for a phosphorylation-based mechanism which regulates specific Oct4 homodimer conformations. Point mutations of a putative phosphorylation site can specifically abrogate transcriptional activity of a specific homodimer assembly, with little effect on other configurations. Moreover, we performed bioinformatic predictions to identify a subset of Oct4 target genes which may be regulated by this specific assembly, and show that altering Oct4 protein levels affects transcription of Oct4 target genes which are regulated by this assembly but not others. Finally, we identified several signaling pathways which may mediate this phosphorylation and act in combination to regulate Oct4 transcriptional activity and protein stability. These results provide a mechanism for rapid and reversible alteration of Oct4 transactivation potential in response to extracellular signals.
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影响因子：
64.5
作者：
Mitsui, K;Tokuzawa, Y;Yamanaka, S
通讯作者：
Yamanaka, S
通过表达分析在胚胎干细胞中解剖OCT3/4调节的基因网络。
影响因子：
3.7
作者：
Matoba, Ryo;Niwa, Hitoshi;Masui, Shinji;Ohtsuka, Satoshi;Carter, Mark G.;Sharov, Alexei A.;Ko, Minoru S. H.
通讯作者：
Ko, Minoru S. H.
影响因子：
2.7
作者：
PALMIERI, SL;PETER, W;SCHOLER, HR
通讯作者：
SCHOLER, HR
影响因子：
5.3
作者：
Gu, Peili;Le Menuet, Damien;Cooney, Austin J.
通讯作者：
Cooney, Austin J.
影响因子：
4.8
作者：
Christensen, AE;Selheim, F;Doskeland, SO
通讯作者：
Doskeland, SO