HDAC8 regulates protein kinase D phosphorylation in skeletal myoblasts in response to stress signaling

Skeletal muscle differentiation involves activation of quiescent satellite cells to proliferate, differentiate and fuse to form new myofibers; this requires coordination of myogenic transcription factors. Myogenic transcription is tightly regulated by various intracellular signaling pathways, which include members of the protein kinase D (PKD) family. PKD is a family of serine-threonine kinases that regulate gene expression, protein secretion, cell proliferation, differentiation and inflammation. PKD is a unique PKC family member that shares distant sequence homology to calcium-regulated kinases and plays an important role in muscle physiology. In this report, we show that class I histone deacetylase (HDAC) inhibition, and in particular HDAC8 inhibition, attenuated PKD phosphorylation in skeletal C2C12 myoblasts in response to phorbol ester, angiotensin II and dexamethasone signaling independent of changes in total PKD protein expression. As class I HDACs and PKD signaling are requisite for myocyte differentiation, these data suggest that HDAC8 functions as a potential feedback regulator of PKD phosphorylation to control myogenic gene expression.(c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Skeletal muscle differentiation requires the activation of satellite cells to proliferate, differentiate, and fuse. This process is regulated by myogenic transcription factors, which are tightly controlled by intracellular signaling pathways, including the protein kinase D (PKD) family. In this study, the researchers found that inhibiting class I histone deacetylases (HDACs), specifically HDAC8, attenuated PKD phosphorylation in skeletal muscle cells, suggesting that HDAC8 may function as a feedback regulator of PKD phosphorylation during muscle differentiation.