Ubiquitin ligases HUWE1 and NEDD4 cooperatively control signal-dependent PRC2-Ezh1?/?-mediated adaptive stress response pathway in skeletal muscle cells.

ABSTRACT:

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-Ezh1?/? signaling pathway from cytoplasm to chromatin protects skeletal muscle cells from oxidative stress. However, detailed mechanisms controlling degradation of cytoplasmic Ezh1? and assembly of canonical PRC2-Ezh1? repressive complex remain to be clarified.

Results

Here, we report NEDD4 ubiquitin E3 ligase, as key regulator of Ezh1?. In addition, we report that ubiquitination and degradation of Ezh1? is controlled by another layer of regulation, that is, one specific phosphorylation of serine 560 located at Ezh1?-specific C terminal. Finally, we demonstrate that also Ezh1? 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-Ezh1?/? pathway to direct modulation of epigenome plasticity and transcriptional output in skeletal muscle cells.

SUBMITTER: Liu P 

PROVIDER: S-EPMC6921592 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature