Phosphorylation of Sox2 Cooperates in Reprogramming to Pluripotent Stem Cells
Phosphorylation of Sox2 Cooperates in Reprogramming to Pluripotent Stem Cells
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DOI：
10.1002/stem.540
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发表时间：
2010-12-01
期刊：
影响因子：
5.2
通讯作者：
Dong, Zigang
中科院分区：
文献类型：
--
作者：
Jeong, Chul-Ho;Cho, Yong-Yeon;Dong, Zigang
体细胞可以通过转导重编程因子（包括Oct 4、Sox 2、Klf 4和c-Myc）重编程为诱导多能干细胞（iPSC）。这些因子的协调网络被认为赋予了iPSC的多能性。与Oct 4一起，Sox 2作为ESC中的主调节器发挥着重要作用。然而，Sox 2促进自我更新或重编程过程的潜在机制仍有待确定。在这里，我们提供了新的证据磷酸化为基础的调节Sox 2的活动。Akt直接与Sox 2相互作用，并通过Thr 118磷酸化促进其稳定，从而增强Sox 2在ESCs中的转录活性。此外，Sox 2的磷酸化通过使得能够更有效地诱导iPSC而在小鼠胚胎成纤维细胞的重编程中协作。总的来说，我们的研究为Sox 2在ESCs中的调控机制提供了新的见解，也提供了磷酸化事件和体细胞重编程之间的直接联系。干细胞2010; 28：2141-2150
Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by transduction of reprogramming factors, including Oct4, Sox2, Klf4, and c-Myc. A coordinated network of these factors was suggested to confer a pluripotency of iPSCs. Together with Oct4, Sox2 plays a major role as a master regulator in ESCs. However, the underlying mechanisms by which Sox2 contributes to self-renewal or reprogramming processes remain to be determined. Here, we provide new evidence for a phosphorylation-based regulation of Sox2 activity. Akt directly interacts with Sox2 and promotes its stabilization through phosphorylation at Thr118, which enhances the transcriptional activity of Sox2 in ESCs. Moreover, phosphorylation of Sox2 cooperates in the reprogramming of mouse embryonic fibroblasts by enabling more efficient induction of iPSCs. Overall, our studies provide new insights into the regulatory mechanism of Sox2 in ESCs and also provide a direct link between phosphorylation events and somatic cell reprogramming. STEM CELLS 2010; 28: 2141-2150