Myostatin induces p300 degradation to silence cyclin D1 expression through the PI3K/PTEN/Akt pathway
Myostatin induces p300 degradation to silence cyclin D1 expression through the PI3K/PTEN/Akt pathway
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肌肉生长抑制素通过 PI3K/PTEN/Akt 途径诱导 p300 降解以沉默细胞周期蛋白 D1 表达
DOI：
10.1016/j.cellsig.2008.03.013
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发表时间：
2008-08-01
影响因子：
4.8
通讯作者：
Zhu, Dahai
中科院分区：
文献类型：
--
作者：
Ji, Ming;Zhang, Qiang;Zhu, Dahai
肌肉生长抑制素是骨骼肌生长的负调控因子，影响与细胞增殖、分化和代谢有关的众多基因的表达。然而，肌肉生长抑制素调控基因表达的分子机制仍有待阐明。在本研究中，我们发现myostatin阻断了p300对细胞周期蛋白d1启动子的募集，导致细胞周期蛋白d1表达的沉默。我们的数据进一步表明，myostatin通过泛素-蛋白酶体系统诱导p300的降解，从而降低了p300的蛋白水平。此外，我们还提供了实验证据，表明肌肉抑制素诱导的p300降解是由磷脂酰肌醇3-激酶/PTEN/Akt信号通路介导的，这一过程可被IGF-1或胰岛素拮抗。这项研究的结果揭示了对肌肉生长抑素反应的基因表达的表观遗传控制。(C)2008 Elsevier Inc.保留所有权利。
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.