Oncogenic Ha-Ras-induced Signaling Activates NF-κB Transcriptional Activity, Which Is Required for Cellular Transformation

作者：Timothy Scott Finco, John K. Westwick, Jacqueline L. Norris, Amer A. Beg, Channing J. Der, Albert S. Baldwin · 发表于：Journal of Biological Chemistry · 年份：1997 · DOI：10.1074/jbc.272.39.24113 · 被引用次数：377 · 研究领域：NF-κB Signaling Pathways、Cell death mechanisms and regulation、Cytokine Signaling Pathways and Interactions

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-kappaB has been widely studied as a regulator of genes involved in immune and inflammatory responses. A variety of stimuli activate NF-kappaB through the induced phosphorylation and degradation of the inhibitor IkappaB followed by nuclear translocation of NF-kappaB. We show here that oncogenic forms of Ha-Ras activate NF-kappaB, not through induced nuclear translocation, but rather through the activation of the transcriptional function of the NF-kappaB RelA/p65 subunit. Importantly, RelA/p65 -/- cells are inefficient in the activation of kappaB-dependent gene expression in response to oncogenic Ras expression. Furthermore, IkappaBalpha expression blocks focus formation in NIH3T3 cells induced by oncogenic Ras. These results demonstrate that NF-kappaB is a critical downstream mediator of Ha-Ras signaling and oncogenic potential.