NF-KAPPA-B ACTIVATION BY ULTRAVIOLET-LIGHT NOT DEPENDENT ON A NUCLEAR SIGNAL

NF-KAPPA-B ACTIVATION BY ULTRAVIOLET-LIGHT NOT DEPENDENT ON A NUCLEAR SIGNAL
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DOI:
10.1126/science.8367725
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发表时间:
1993-09-10
期刊:
影响因子:
56.9
通讯作者:
KARIN, M
KARIN, M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
DEVARY, Y;ROSETTE, C;KARIN, M

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哺乳动物细胞暴露于辐射会触发紫外线(UV)反应,其中包括激活蛋白1 (AP-1)和核因子κ B (nf - κ B)的激活。这被认为是由受损DNA诱导的核信号级联引起的。最近,UV诱导AP-1的途径被证明是由Src酪氨酸激酶和Ha-Ras小鸟苷三磷酸结合蛋白介导的,这些蛋白位于质膜上。这里证明了相同的途径介导NF-kappaB被紫外线诱导。由于失活的NF-kappaB储存在细胞质中,对其活化的分析直接测试了核启动信号级联的参与。在NF-kappaB诱导和另一个关键信号事件的激活中,去核细胞对紫外线完全响应。因此,紫外线反应不需要在细胞核中产生信号,而可能在质膜处或附近启动。
Exposure of mammalian cells to radiation triggers the ultraviolet (UV) response, which includes activation of activator protein-1 (AP-1) and nuclear factor kappa B (NF-kappaB). This was postulated to occur by induction of a nuclear signaling cascade by damaged DNA. Recently, induction of AP-1 by UV was shown to be mediated by a pathway involving Src tyrosine kinases and the Ha-Ras small guanosine triphosphate-binding protein, proteins located at the plasma membrane. It is demonstrated here that the same pathway mediates induction of NF-kappaB by UV. Because inactive NF-kappaB is stored in the cytosol, analysis of its activation directly tests the involvement of a nuclear-initiated signaling cascade. Enucleated cells are fully responsive to UV both in NF-kappaB induction and in activation of another key signaling event. Therefore, the UV response does not require a signal generated in the nucleus and is likely to be initiated at or near the plasma membrane.