Cargando…
Ubiquitin ligases HUWE1 and NEDD4 cooperatively control signal-dependent PRC2-Ezh1α/β-mediated adaptive stress response pathway in skeletal muscle cells
BACKGROUND: While the role of Polycomb group protein-mediated “cell memory” is well established in developmental contexts, little is known about their role in adult tissues and in particular in post-mitotic cells. Emerging evidence assigns a pivotal role in cell plasticity and adaptation. PRC2-Ezh1α...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921592/ https://www.ncbi.nlm.nih.gov/pubmed/31856907 http://dx.doi.org/10.1186/s13072-019-0322-5 |
_version_ | 1783481194718953472 |
---|---|
author | Liu, Peng Shuaib, Muhammad Zhang, Huoming Nadeef, Seba Orlando, Valerio |
author_facet | Liu, Peng Shuaib, Muhammad Zhang, Huoming Nadeef, Seba Orlando, Valerio |
author_sort | Liu, Peng |
collection | PubMed |
description | BACKGROUND: While the role of Polycomb group protein-mediated “cell memory” is well established in developmental contexts, little is known about their role in adult tissues and in particular in post-mitotic cells. Emerging evidence assigns a pivotal role in cell plasticity and adaptation. PRC2-Ezh1α/β signaling pathway from cytoplasm to chromatin protects skeletal muscle cells from oxidative stress. However, detailed mechanisms controlling degradation of cytoplasmic Ezh1β and assembly of canonical PRC2-Ezh1α repressive complex remain to be clarified. RESULTS: Here, we report NEDD4 ubiquitin E3 ligase, as key regulator of Ezh1β. In addition, we report that ubiquitination and degradation of Ezh1β is controlled by another layer of regulation, that is, one specific phosphorylation of serine 560 located at Ezh1β-specific C terminal. Finally, we demonstrate that also Ezh1α needs to be stabilized under stress condition and this stabilization process requires decreased association pattern between another E3 ubiquitin ligase HUWE1. CONCLUSIONS: Together, these results shed light on key components that regulate PRC2-Ezh1α/β pathway to direct modulation of epigenome plasticity and transcriptional output in skeletal muscle cells. |
format | Online Article Text |
id | pubmed-6921592 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-69215922019-12-30 Ubiquitin ligases HUWE1 and NEDD4 cooperatively control signal-dependent PRC2-Ezh1α/β-mediated adaptive stress response pathway in skeletal muscle cells Liu, Peng Shuaib, Muhammad Zhang, Huoming Nadeef, Seba Orlando, Valerio Epigenetics Chromatin Research BACKGROUND: While the role of Polycomb group protein-mediated “cell memory” is well established in developmental contexts, little is known about their role in adult tissues and in particular in post-mitotic cells. Emerging evidence assigns a pivotal role in cell plasticity and adaptation. PRC2-Ezh1α/β signaling pathway from cytoplasm to chromatin protects skeletal muscle cells from oxidative stress. However, detailed mechanisms controlling degradation of cytoplasmic Ezh1β and assembly of canonical PRC2-Ezh1α repressive complex remain to be clarified. RESULTS: Here, we report NEDD4 ubiquitin E3 ligase, as key regulator of Ezh1β. In addition, we report that ubiquitination and degradation of Ezh1β is controlled by another layer of regulation, that is, one specific phosphorylation of serine 560 located at Ezh1β-specific C terminal. Finally, we demonstrate that also Ezh1α needs to be stabilized under stress condition and this stabilization process requires decreased association pattern between another E3 ubiquitin ligase HUWE1. CONCLUSIONS: Together, these results shed light on key components that regulate PRC2-Ezh1α/β pathway to direct modulation of epigenome plasticity and transcriptional output in skeletal muscle cells. BioMed Central 2019-12-19 /pmc/articles/PMC6921592/ /pubmed/31856907 http://dx.doi.org/10.1186/s13072-019-0322-5 Text en © The Author(s) 2019 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Liu, Peng Shuaib, Muhammad Zhang, Huoming Nadeef, Seba Orlando, Valerio Ubiquitin ligases HUWE1 and NEDD4 cooperatively control signal-dependent PRC2-Ezh1α/β-mediated adaptive stress response pathway in skeletal muscle cells |
title | Ubiquitin ligases HUWE1 and NEDD4 cooperatively control signal-dependent PRC2-Ezh1α/β-mediated adaptive stress response pathway in skeletal muscle cells |
title_full | Ubiquitin ligases HUWE1 and NEDD4 cooperatively control signal-dependent PRC2-Ezh1α/β-mediated adaptive stress response pathway in skeletal muscle cells |
title_fullStr | Ubiquitin ligases HUWE1 and NEDD4 cooperatively control signal-dependent PRC2-Ezh1α/β-mediated adaptive stress response pathway in skeletal muscle cells |
title_full_unstemmed | Ubiquitin ligases HUWE1 and NEDD4 cooperatively control signal-dependent PRC2-Ezh1α/β-mediated adaptive stress response pathway in skeletal muscle cells |
title_short | Ubiquitin ligases HUWE1 and NEDD4 cooperatively control signal-dependent PRC2-Ezh1α/β-mediated adaptive stress response pathway in skeletal muscle cells |
title_sort | ubiquitin ligases huwe1 and nedd4 cooperatively control signal-dependent prc2-ezh1α/β-mediated adaptive stress response pathway in skeletal muscle cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921592/ https://www.ncbi.nlm.nih.gov/pubmed/31856907 http://dx.doi.org/10.1186/s13072-019-0322-5 |
work_keys_str_mv | AT liupeng ubiquitinligaseshuwe1andnedd4cooperativelycontrolsignaldependentprc2ezh1abmediatedadaptivestressresponsepathwayinskeletalmusclecells AT shuaibmuhammad ubiquitinligaseshuwe1andnedd4cooperativelycontrolsignaldependentprc2ezh1abmediatedadaptivestressresponsepathwayinskeletalmusclecells AT zhanghuoming ubiquitinligaseshuwe1andnedd4cooperativelycontrolsignaldependentprc2ezh1abmediatedadaptivestressresponsepathwayinskeletalmusclecells AT nadeefseba ubiquitinligaseshuwe1andnedd4cooperativelycontrolsignaldependentprc2ezh1abmediatedadaptivestressresponsepathwayinskeletalmusclecells AT orlandovalerio ubiquitinligaseshuwe1andnedd4cooperativelycontrolsignaldependentprc2ezh1abmediatedadaptivestressresponsepathwayinskeletalmusclecells |