Pcid2 Inactivates Developmental Genes in Human and Mouse Embryonic Stem Cells to Sustain Their Pluripotency by Modulation of EID1 Stability
Pcid2 Inactivates Developmental Genes in Human and Mouse Embryonic Stem Cells to Sustain Their Pluripotency by Modulation of EID1 Stability
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Pcid2 灭活人类和小鼠胚胎干细胞中的发育基因，通过调节 EID1 稳定性来维持其多能性
作者：
Ye Buqing;Dai Zhonghua;Liu Benyu;Wang Rui;Li Chong;Huang Guanling;Wang Shuo;Xia Pengyan;Yang Xuan;Kuwahara Kazuhiko;Sakaguchi Nobuo;Fan Zusen
自我更新和分化是胚胎干细胞（ESCs）的标志。然而，它在很大程度上是未知的多能性是如何调节的。在这里，我们证明，PAP 2是需要在小鼠和人类胚胎干细胞的自我更新的维护。PAP 2在抑制ESC分化中起关键作用。PAP 2缺乏导致胚泡阶段之前的早期胚胎死亡。P300 2与EID 1结合，存在于ESCs中的CBP/p300-EID 1复合物中。我们发现MDM 2是一种E3连接酶，用于K48连接的EID 1泛素化降解。为了维持自我更新，PAD 2与EID 1结合以阻止与MDM 2的结合。EID 1不被降解，维持其稳定性，从而阻断CBP/p300的HAT活性，导致发育基因表达的抑制。总的来说，PAP 2存在于CBP/p300-EID 1复合物中，通过调节EID 1降解来控制小鼠和人ESC的开关平衡。干细胞2014;32：623-635
Self-renewal and differentiation are the hallmarks of embryonic stem cells (ESCs). However, it is largely unknown about how the pluripotency is regulated. Here we demonstrate that Pcid2 is required for the maintenance of self-renewal both in mouse and human ESCs. Pcid2 plays a critical role in suppression of ESC differentiation. Pcid2 deficiency causes early embryonic lethality before the blastocyst stage. Pcid2 associates with EID1 and is present in the CBP/p300-EID1 complex in the ESCs. We show that MDM2 is an E3 ligase for K48-linked EID1 ubiquitination for its degradation. For the maintenance of self-renewal, Pcid2 binds to EID1 to impede the association with MDM2. Then EID1 is not degraded to sustain its stability to block the HAT activity of CBP/p300, leading to suppression of the developmental gene expression. Collectively, Pcid2 is present in the CBP/p300-EID1 complex to control the switch balance of mouse and human ESCs through modulation of EID1 degradation. StemCells2014;32:623–635