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The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via stabilization of Nanog
Nanog is a master pluripotency factor of embryonic stem cells (ESCs). Stable expression of Nanog is essential to maintain the stemness of ESCs. However, Nanog is a short-lived protein and quickly degraded by the ubiquitin-dependent proteasome system. Here we report that the deubiquitinase USP21 inte...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133637/ https://www.ncbi.nlm.nih.gov/pubmed/27886188 http://dx.doi.org/10.1038/ncomms13594 |
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author | Jin, Jiali Liu, Jian Chen, Cong Liu, Zhenping Jiang, Cong Chu, Hongshang Pan, Weijuan Wang, Xinbo Zhang, Lingqiang Li, Bin Jiang, Cizhong Ge, Xin Xie, Xin Wang, Ping |
author_facet | Jin, Jiali Liu, Jian Chen, Cong Liu, Zhenping Jiang, Cong Chu, Hongshang Pan, Weijuan Wang, Xinbo Zhang, Lingqiang Li, Bin Jiang, Cizhong Ge, Xin Xie, Xin Wang, Ping |
author_sort | Jin, Jiali |
collection | PubMed |
description | Nanog is a master pluripotency factor of embryonic stem cells (ESCs). Stable expression of Nanog is essential to maintain the stemness of ESCs. However, Nanog is a short-lived protein and quickly degraded by the ubiquitin-dependent proteasome system. Here we report that the deubiquitinase USP21 interacts with, deubiquitinates and stabilizes Nanog, and therefore maintains the protein level of Nanog in mouse ESCs (mESCs). Loss of USP21 results in Nanog degradation, mESCs differentiation and reduces somatic cell reprogramming efficiency. USP21 is a transcriptional target of the LIF/STAT3 pathway and is downregulated upon differentiation. Moreover, differentiation cues promote ERK-mediated phosphorylation and dissociation of USP21 from Nanog, thus leading to Nanog degradation. In addition, USP21 is recruited to gene promoters by Nanog to deubiquitinate histone H2A at K119 and thus facilitates Nanog-mediated gene expression. Together, our findings provide a regulatory mechanism by which extrinsic signals regulate mESC fate via deubiquitinating Nanog. |
format | Online Article Text |
id | pubmed-5133637 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51336372016-12-21 The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via stabilization of Nanog Jin, Jiali Liu, Jian Chen, Cong Liu, Zhenping Jiang, Cong Chu, Hongshang Pan, Weijuan Wang, Xinbo Zhang, Lingqiang Li, Bin Jiang, Cizhong Ge, Xin Xie, Xin Wang, Ping Nat Commun Article Nanog is a master pluripotency factor of embryonic stem cells (ESCs). Stable expression of Nanog is essential to maintain the stemness of ESCs. However, Nanog is a short-lived protein and quickly degraded by the ubiquitin-dependent proteasome system. Here we report that the deubiquitinase USP21 interacts with, deubiquitinates and stabilizes Nanog, and therefore maintains the protein level of Nanog in mouse ESCs (mESCs). Loss of USP21 results in Nanog degradation, mESCs differentiation and reduces somatic cell reprogramming efficiency. USP21 is a transcriptional target of the LIF/STAT3 pathway and is downregulated upon differentiation. Moreover, differentiation cues promote ERK-mediated phosphorylation and dissociation of USP21 from Nanog, thus leading to Nanog degradation. In addition, USP21 is recruited to gene promoters by Nanog to deubiquitinate histone H2A at K119 and thus facilitates Nanog-mediated gene expression. Together, our findings provide a regulatory mechanism by which extrinsic signals regulate mESC fate via deubiquitinating Nanog. Nature Publishing Group 2016-11-25 /pmc/articles/PMC5133637/ /pubmed/27886188 http://dx.doi.org/10.1038/ncomms13594 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Jin, Jiali Liu, Jian Chen, Cong Liu, Zhenping Jiang, Cong Chu, Hongshang Pan, Weijuan Wang, Xinbo Zhang, Lingqiang Li, Bin Jiang, Cizhong Ge, Xin Xie, Xin Wang, Ping The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via stabilization of Nanog |
title | The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via stabilization of Nanog |
title_full | The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via stabilization of Nanog |
title_fullStr | The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via stabilization of Nanog |
title_full_unstemmed | The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via stabilization of Nanog |
title_short | The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via stabilization of Nanog |
title_sort | deubiquitinase usp21 maintains the stemness of mouse embryonic stem cells via stabilization of nanog |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133637/ https://www.ncbi.nlm.nih.gov/pubmed/27886188 http://dx.doi.org/10.1038/ncomms13594 |
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