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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Bcl-2 is the target of a UV-inducible apoptosis switch and a node for UV signaling
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Bcl-2 is the target of a UV-inducible apoptosis switch and a node for UV signaling

机译：Bcl-2是紫外线诱导的细胞凋亡开关的目标，是紫外线信号转导的节点

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摘要

Sunlight's UVB radiation triggers cell signaling at multiple sites to induce apoptosis. The integration of these signal entry sites is not understood. Here we show that P53 and E2f1 constitute a UV-inducible apoptosis switch. At low-UV doses, wild-type cells resemble the OFF state of an siP53-treated cell, whereas at high-UV doses, the apoptosis frequency transitions to the fully ON behavior of an siE2f1-treated cell. The switch's target is Bcl-2: Rapid Bcl-2 down-regulation in response to UVB-induced DNA photoproducts is lost in P53-deficient cells, but, as for apoptosis, is restored when both P53 and its inhibited target E2f1 are absent. P53's down-regulation of Bcl-2 is mediated entirely through E2f1. Bcl-2 is also down-regulated by a separate pathway triggered by DNA photo-products in the absence of P53 and E2f1. Four UV pathways terminating on Bcl-2 contribute to apoptosis after UVB irradiation. The apoptosis lost in p53~(-/-) is completely restored by siBcl-2, implying that Bcl-2 is a rate-limiting member of this network. These results identify Bcl-2 as an integrator of several UV-induced proapo-ptotic signals and show that it, in turn, suppresses a direct UV-apoptosis pathway. UV-induced apoptosis requires both UV activation of the direct pathway and a separate UV disinhibition of this pathway through P53-E2f1-Bcl-2.
机译：阳光的紫外线辐射会在多个位置触发细胞信号传导，从而诱导细胞凋亡。这些信号进入位点的整合尚不清楚。在这里，我们显示P53和E2f1构成了紫外线诱导的凋亡开关。在低紫外线剂量下，野生型细胞类似于siP53处理的细胞的OFF状态，而在高紫外线剂量下，凋亡频率转变为siE2f1处理的细胞的完全ON行为。开关的目标是Bcl-2：在缺乏P53的细胞中，响应UVB诱导的DNA光产物而迅速Bcl-2下调消失了，但是，对于凋亡，当P53及其抑制的目标E2f1都不存在时，恢复了。 P53对Bcl-2的下调完全通过E2f1介导。在不存在P53和E2f1的情况下，Bcl-2也被DNA光产物触发的单独途径下调。终止于Bcl-2的四个UV途径有助于UVB照射后的细胞凋亡。 siBcl-2完全恢复了p53〜（-/-）中丢失的细胞凋亡，这表明Bcl-2是该网络的限速成员。这些结果表明Bcl-2是几种紫外线诱导的促凋亡信号的整合剂，并表明它进而抑制了直接的紫外线凋亡途径。 UV诱导的细胞凋亡既需要直接途径的UV激活，又需要通过P53-E2f1-Bcl-2对该途径的单独UV抑制。

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