The oncoprotein LMP1 mimics an activated CD40 receptor, yet it is not known whether constitutive CD40 signaling, like LMP1, is sufficient to transform cells. Here we demonstrate that constitutive activation of the CD40 pathway by a chimeric LMP1CD40 molecule resembles the transforming function of LMP1 in inducing loss of contact inhibition and anchorage independent growth of Rat1 fibroblasts. Rat1 transformation correlates with the expression level of LMP1CD40 and depends on its ability to oligomerize. Our data provide direct evidence for the oncogenic potential of the CD40 signaling pathway, which is also established as a model-mechanism for LMP1-induced transformation.

译文

:癌蛋白LMP1模仿激活的CD40受体,但尚不知道本构性CD40信号是否像LMP1一样足以转化细胞。在这里,我们证明了嵌合LMP1CD40分子对CD40途径的组成性激活类似于LMP1的转化功能,可诱导Rat1成纤维细胞失去接触抑制和锚定非依赖性生长。 Rat1转化与LMP1CD40的表达水平相关,并取决于其寡聚能力。我们的数据为CD40信号传导途径的致癌潜力提供了直接证据,该途径也被确立为LMP1诱导转化的模型机制。

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