Biomolecular Dynamics Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka, 565-0871 Japan.
J Biol Chem. 2013 May 24;288(21):15085-97. doi: 10.1074/jbc.M112.448837. Epub 2013 Apr 11.
Oct4 is a member of the POU family of transcription factors and plays a critical role in both maintenance of the undifferentiated state of embryonic stem (ES) cells and in the reprogramming of somatic cells to induced pluripotent stem cells. Oct4 is imported into the nucleus where it functions as a transcription factor; however, the spatiotemporal dynamic behavior of Oct4 remains largely unknown. In the present study we show that Oct4 is a nucleocytoplasmic shuttling protein. Furthermore, although Oct4 mutants with altered nuclear import/export activity were able to maintain the self-renewal of ES cells, they displayed limited potential for cellular reprogramming. These results indicate that the intracellular localization of Oct4, which is dependent on nucleocytoplasmic shuttling, must be more strictly regulated for cellular reprogramming, suggesting that Oct4 plays differential roles in the self-renewal of ES cells and in somatic cell reprogramming.
Oct4 是 POU 家族转录因子的一员，在维持胚胎干细胞（ES）的未分化状态和体细胞重编程为诱导多能干细胞方面发挥着关键作用。Oct4 被导入细胞核内，在那里它作为转录因子发挥作用；然而，Oct4 的时空动态行为在很大程度上仍然未知。在本研究中，我们表明 Oct4 是一种核质穿梭蛋白。此外，尽管具有改变核输入/输出活性的 Oct4 突变体能够维持 ES 细胞的自我更新，但它们在细胞重编程方面的潜力有限。这些结果表明，Oct4 的细胞内定位依赖于核质穿梭，对于细胞重编程必须有更严格的调控，这表明 Oct4 在 ES 细胞的自我更新和体细胞重编程中发挥着不同的作用。
