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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Myocardin inhibits cellular proliferation by inhibiting NF-κB(p65)-dependent cell cycle progression
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Myocardin inhibits cellular proliferation by inhibiting NF-κB(p65)-dependent cell cycle progression

机译：心肌素通过抑制依赖于NF-κB（p65）的细胞周期进程来抑制细胞增殖

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摘要

We previously reported the importance of the serum response factor (SRF) cofactor myocardin in controlling muscle gene expression as well as the fundamental role for the inflammatory transcription factor NF-κB in governing cellular fate. Inactivation of myocardin has been implicated in malignant tumor growth. However, the underlying mechanism of myocardin regulation of cellular growth remains unclear. Here we show that NF-κB(p65) represses myocardin activation of cardiac and smooth muscle genes in a CArG-box-dependent manner. Consistent with their functional interaction, p65 directly interacts with myocardin and inhibits the formation of the myocardin/SRF/CArG ternary complex in vitro and in vivo. Conversely, myocardin decreases p65-mediated target gene activation by interfering with p65 DNA binding and abrogates LPS-induced TNF-α expression. Importantly, myocardin inhibits cellular proliferation by interfering with NF-κB-dependent cell-cycle regulation. Cumulatively, these findings identify a function for myocardin as an SRF-independent transcriptional repressor and cell-cycle regulator and provide a molecular mechanism by which interaction between NF-κB and myocardin plays a central role in modulating cellular proliferation and differentiation.
机译：我们之前曾报道过血清反应因子（SRF）辅助因子心肌素在控制肌肉基因表达中的重要性以及炎症转录因子NF-κB在控制细胞命运中的基本作用。心肌素的失活与恶性肿瘤的生长有关。但是，心肌细胞调节细胞生长的基本机制仍不清楚。在这里，我们显示NF-κB（p65）以CArG-box依赖性方式抑制心肌和平滑肌基因的心肌激活。与它们的功能相互作用一致，p65在体外和体内直接与心肌素相互作用，并抑制心肌素/ SRF / CArG三元复合物的形成。相反，心肌素通过干扰p65 DNA结合来降低p65介导的靶基因激活，并消除LPS诱导的TNF-α表达。重要的是，心肌素通过干扰依赖于NF-κB的细胞周期调节来抑制细胞增殖。累积地，这些发现确定了心肌素作为独立于SRF的转录阻遏物和细胞周期调节剂的功能，并提供了一种分子机制，通过该分子机制，NF-κB与心肌素之间的相互作用在调节细胞增殖和分化中起着核心作用。

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