The Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.
Stem Cells. 2010 Dec;28(12):2141-50. doi: 10.1002/stem.540.
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.
体细胞可以通过转导重编程因子（包括 Oct4、Sox2、Klf4 和 c-Myc）被重编程为诱导多能干细胞（iPSCs）。这些因子的协调网络被认为赋予了 iPSCs 的多能性。与 Oct4 一起，Sox2 作为 ESCs 中的主要调控因子发挥重要作用。然而，Sox2 如何有助于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 Sox2 活性基于磷酸化调节的新证据。Akt 直接与 Sox2 相互作用，并通过 Thr118 的磷酸化促进其稳定，从而增强 Sox2 在 ESCs 中的转录活性。此外，Sox2 的磷酸化通过更有效地诱导 iPSCs 来协同重编程小鼠胚胎成纤维细胞。总的来说，我们的研究为 Sox2 在 ESCs 中的调控机制提供了新的见解，并为磷酸化事件与体细胞重编程之间建立了直接联系。
