Oncogenic Ha-Ras-induced signaling activates NF-kappa B transcriptional activity, which is required for cellular transformation
Oncogenic Ha-Ras-induced signaling activates NF-kappa B transcriptional activity, which is required for cellular transformation
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DOI：
10.1074/jbc.272.39.24113
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发表时间：
1997-09-26
影响因子：
4.8
通讯作者：
Baldwin, AS
中科院分区：
文献类型：
--
作者：
Finco, TS;Westwick, JK;Baldwin, AS
Ras蛋白通过激活Raf依赖性和Raf非依赖性信号转导途径以及随后激活特异性转录因子来刺激细胞增殖和分化。转录因子NF-κ B B作为参与免疫和炎症反应的基因的调节剂已被广泛研究，多种刺激物通过诱导抑制剂I κ B的磷酸化和降解，随后NF-κ B的核转位来激活NF-κ B。我们在此表明，Ha-Ras的致癌形式激活NF-κ B，不是通过诱导的核转位，而是通过激活NF-κ B RelA/p65亚基的转录功能。重要的是，RelA/p65 -/-细胞在响应致癌Ras表达的κ B依赖性基因表达的激活中是无效的。此外，I κ B α表达阻断致癌Ras诱导的NIH 3 T3细胞中的病灶形成。这些结果表明NF-κ B是Ha-Ras信号传导和致癌潜力的关键下游介质。
Ras proteins function in stimulating cell proliferation and differentiation through the activation of Raf-dependent and Raf independent signal transduction pathways and the subsequent activation of specific transcription factors, The transcription factor NF-kappa B has been widely studied as a regulator of genes involved in immune and inflammatory responses, A variety of stimuli activate NF-kappa B through the induced phosphorylation and degradation of the inhibitor I kappa B followed by nuclear translocation of NF-kappa B. We show here that oncogenic forms of Ha-Ras activate NF-kappa B, not through induced nuclear translocation, but rather through the activation of the transcriptional function of the NF-kappa B RelA/p65 subunit, Importantly, RelA/p65 -/- cells are inefficient in the activation of kappa B-dependent gene expression in response to oncogenic Ras expression, Furthermore, I kappa B alpha expression blocks focus formation in NIH3T3 cells induced by oncogenic Ras, These results demonstrate that NF-kappa B is a critical downstream mediator of Ha-Ras signaling and oncogenic potential.