p38α MAP kinase as a sensor of reactive oxygen species in tumorigenesis
p38α MAP kinase as a sensor of reactive oxygen species in tumorigenesis
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DOI：
10.1016/j.ccr.2006.12.013
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发表时间：
2007-02-01
期刊：
影响因子：
50.3
通讯作者：
Nebreda, Angel R.
中科院分区：
文献类型：
--
作者：
Dolado, Ignacio;Swat, Aneta;Nebreda, Angel R.
p38 α是一种应激激活的蛋白激酶，其负调控致癌H-Ras诱导的恶性转化，尽管所涉及的机制尚未完全了解。在这里，我们表明，p38 α不是一个致癌信号的一般抑制剂，但它特异性地调节转化诱导的癌基因产生活性氧（ROS）。这种抑制作用是由于在转化过程的早期ROS诱导的p38 α活化，其诱导细胞凋亡并防止ROS的积累及其致癌作用。因此，高度致瘤性的癌细胞系已经开发出将p38 α活化与ROS产生解偶联的机制。我们的研究结果表明，氧化应激传感起着关键作用，抑制肿瘤的启动p38 α。
p38 alpha is a stress-activated protein kinase that negatively regulates malignant transformation induced by oncogenic H-Ras, although the mechanisms involved are not fully understood. Here, we show that p38 alpha is not a general inhibitor of oncogenic signaling, but that it specifically modulates transformation induced by oncogenes that produce reactive oxygen species (ROS). This inhibitory effect is due to the ROS-induced activation of p38 alpha early in the process of transformation, which induces apoptosis and prevents the accumulation of ROS and their carcinogenic effects. Accordingly, highly tumorigenic cancer cell lines have developed a mechanism to uncouple p38 alpha activation from ROS production. Our results indicate that oxidative stress sensing plays a key role in the inhibition of tumor initiation by p38 alpha.