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模仿活化的CD40受体,但尚不清楚组成型CD40信号传导 (如LMP1) 是否足以转化细胞。在这里,我们证明了嵌合LMP1CD40分子对CD40途径的组成型激活类似于LMP1在诱导Rat1成纤维细胞的接触抑制丧失和锚定独立生长方面的转化功能。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信号通路的致癌潜力提供了直接证据,CD40信号通路也被确立为LMP1-induced转化的模型机制。

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