Pcid2 Inactivates Developmental Genes in Human and Mouse Embryonic Stem Cells to Sustain Their Pluripotency by Modulation of EID1 Stability-Reference-Cited by-同舟云学术

Pcid2 Inactivates Developmental Genes in Human and Mouse Embryonic Stem Cells to Sustain Their Pluripotency by Modulation of EID1 Stability

Published:2014-02-19 Issue:3 Volume:32 Page:623-635
ISSN:1066-5099
Container-title:Stem Cells
language:en
Short-container-title:

Author:

YE Buqing¹,Dai Zhonghua¹,Liu Benyu¹,Wang Rui¹,Li Chong¹,Huang Guanling¹,Wang Shuo¹,Xia Pengyan¹,Yang Xuan¹,Kuwahara Kazuhiko²,Sakaguchi Nobuo²,Fan Zusen¹

Affiliation:

1. Key Laboratory of Infection and Immunity of CAS Institute of Biophysics, Chinese Academy of Sciences, Beijing, People’s Republic of China

2. Department of Immunology Graduate School of Medical Sciences Kumamoto University, Kumamoto, Japan

Abstract

Abstract 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. Stem Cells 2014;32:623–635

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

Link

https://onlinelibrary.wiley.com/doi/pdf/10.1002/stem.1580

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