Oncostatin M induces growth arrest of skeletal muscle cells in G1 phase by regulating cyclin D1 protein level
Oncostatin M induces growth arrest of skeletal muscle cells in G1 phase by regulating cyclin D1 protein level
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DOI：
10.1016/j.cellsig.2007.09.004
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发表时间：
2008-01-01
影响因子：
4.8
通讯作者：
Jo, Sangmee Ahn
中科院分区：
文献类型：
--
作者：
Kim, Hyuck;Jo, Chulman;Jo, Sangmee Ahn
抑癌素M(OSM)是一种IL-6家族细胞因子，根据细胞类型的不同，可抑制或促进细胞的生长。在此，我们报道了OSM通过阻断细胞周期从G(1)期到S期来抑制骨骼肌细胞的增殖。OSM处理显著降低了CDK4特异性磷酸化位点Ser-795的细胞周期蛋白D1蛋白水平和视网膜母细胞瘤蛋白(Rb)的磷酸化水平。OSM诱导的细胞周期蛋白D1的减少与细胞周期蛋白D1/p27(Kip1)复合体的减少和CDK2/p27(Kip1)复合体的增加有关，从而导致CDK2活性的抑制。蛋白酶体抑制剂lactacystin的实验结果表明，细胞周期蛋白D1的减少是通过泛素/蛋白酶体蛋白分解实现的。此外，STAT3的激活，而不是STAT1的激活，可能调节OSM诱导的细胞周期蛋白D1的减少。显性负性(DN)-STAT3可阻断OSM诱导的细胞周期蛋白D1的减少，而结构性激活的-STAT3也可诱导细胞周期蛋白D1的减少。这些结果表明，OSM在G(1)/S检查点阻止了骨骼肌细胞的生长，这一反应是通过泛素/蛋白酶体依赖的细胞周期蛋白D1蛋白减少而发生的，该蛋白受STAT3调节。(C)2007 Elsevier Inc.保留所有权利。
Oncostatin M (OSM), an IL-6 family cytokine, either inhibits or enhances the growth of cells depending on cell type. Here, we report that OSM inhibits proliferation of skeletal muscle cells by blocking cell cycle progression from G(1) to S phase. OSM treatment significantly reduced levels of cyclin D1 protein and phosphorylation of retinoblastoma protein (Rb) at Ser-795, a CDK4-specific phosphorylation site. The OSM-induced cyclin D1 reduction correlated with decreased amount of the cyclin D1/p27(Kip1) complex and increased amounts of the CDK2/p27(Kip1) complex, resulting in inhibition of CDK2 activity. Results obtained with lactacystin, a proteasome inhibitor, demonstrated that cyclin D1 reduction occurred through ubiquitin/proteasome proteolysis. In addition, activation of STAT3, but not STAT1, is likely to regulate OSM-induced cyclin D1 reduction. Dominant negative (DN)-STAT3 blocked OSM-induced cyclin D1 reduction, and constitutively active-STAT3 also induced cyclin D1 reduction. These results suggest that OSM arrests skeletal muscle cell growth at the G(1)/S checkpoint and that this response occurs by an ubiquitin/proteasome-dependent cyclin D1 protein reduction which is regulated by STAT3. (C) 2007 Elsevier Inc. All rights reserved.