Journal
CELLULAR SIGNALLING
Volume 20, Issue 8, Pages 1452-1458Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2008.03.013
Keywords
myostatin; Akt; p300; histone acetylation
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Myostatin is a negative regulator of skeletal muscle growth and affects numerous genes expression involved in cell proliferation, differentiation and metabolism. However, the molecular mechanisms underlying myostatin-regulated genes expression remain to be elucidated. In this study, we showed that myostatin blocked the recruitment of p300 to the cyclin D1 promoter, resulting in the silence of cyclin D1 expression. Our data further demonstrated that myostatin decreased the protein level of p300 by inducing p300 degradation via the ubiquitin-proteasome system. In addition, we provided experimental evidence to show that myostatin-induced p300 degradation was mediated by the phosphatidylinositol 3-kinase/PTEN/Akt signaling pathway and this could be antagonized by IGF-1 or insulin. Results presented in this study uncovered an epigenetic control of genes expression in response to myostatin. (c) 2008 Elsevier Inc. All rights reserved.
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