The signaling adaptor p62 is an important NF-κB mediator in tumorigenesis
The signaling adaptor p62 is an important NF-κB mediator in tumorigenesis
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DOI：
10.1016/j.ccr.2008.02.001
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发表时间：
2008-04-01
期刊：
影响因子：
50.3
通讯作者：
Moscat, Jorge
中科院分区：
文献类型：
--
作者：
Duran, Angeles;Linares, Juan F.;Moscat, Jorge
细胞死亡和存活之间的平衡，致癌转化的两个关键方面，决定了肿瘤发生的结果。核因子-κ B（NF-κ B）是生存的关键调节因子;它由癌基因Ras诱导，当被抑制时，可导致Ras转化细胞的细胞死亡反应。在这里，我们表明信号转导衔接子p62是由Ras诱导的，它的水平在人类肿瘤中增加，并且它是Ras诱导的生存和转化所必需的。p62（-/-）小鼠对Ras诱导的肺腺癌具有抗性。p62是Ras通过肿瘤坏死因子（TNF）受体相关因子6（TRAF 6）的多聚泛素化来触发I κ B激酶（IKK）所必需的，并且其缺陷产生增加的活性氧（ROS）水平，这解释了在p62不存在时Ras的增强的细胞死亡和降低的致瘤性。
The balance between cell death and survival, two critical aspects of oncogenic transformation, determines the outcome of tumorigenesis. Nuclear factor-kappa B (NF-kappa B) is a critical regulator of survival; it is induced by the oncogene Ras and, when inhibited, accounts for the cell death response of Ras-transformed cells. Here, we show that the signaling adaptor p62 is induced by Ras, its levels are increased in human tumors, and it is required for Ras-induced survival and transformation. p62(-/-) mice are resistant to Ras-induced lung adenocarcinomas. p62 is necessary for Ras to trigger I kappa B kinase (IKK) through the polyubiquitination of tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), and its deficiency produces increased reactive oxygen species (ROS) levels, which account for the enhanced cell death and reduced tumorigenicity of Ras in the absence of p62.