László Csaba F, Wu Shiyong
Edison Biotechnology Institute, Ohio University, Athens, OH, USA.
Photochem Photobiol. 2008 Nov-Dec;84(6):1564-8. doi: 10.1111/j.1751-1097.2008.00385.x. Epub 2008 Jun 20.
Nuclear factor-kappa B (NF-kappaB) plays an important role in UV-induced skin tumorigenesis. Activation of NF-kappaB by UV-irradiation is composed of two phases. The early phase culminates with maximal levels of DNA binding ability at 4 h postirradiation and is dependent on translational inhibition. The late-phase activation of NF-kappaB occurs between 16 and 48 h post-irradiation and the mechanism is not clear due to the fact that NF-kappaB was activated in the presence of high level of IkappaBalpha. In this report, we provide evidence that without translational inhibition, the transcription of IkappaBalpha was induced by UV-irradiation. In the late-phase of UV-induced NF-kappaB activation, the IkappaBalpha depletion is the combined result of regulation at both transcriptional and translational levels. Neither ubiquitination nor proteasomal degradation have detectable attributions to IkappaBalpha breakdown. We also demonstrate that UV only induced phosphorylation of p65(S276), while tumor necrosis factor-alpha induced phosphorylation at both Ser276 and 536 sites of p65. Based upon our results, we propose a novel mechanism for translation-regulated IkappaBalpha depletion and MSK-mediated NF-kappaB activation at 24 h post-UV-irradiation.
核因子-κB（NF-κB）在紫外线诱导的皮肤肿瘤发生中起重要作用。紫外线照射激活NF-κB由两个阶段组成。早期阶段在照射后4小时达到DNA结合能力的最高水平，并且依赖于翻译抑制。NF-κB的晚期激活发生在照射后16至48小时之间，由于在高水平的IκBα存在下NF-κB被激活，其机制尚不清楚。在本报告中，我们提供证据表明，在没有翻译抑制的情况下，紫外线照射可诱导IκBα的转录。在紫外线诱导的NF-κB激活的晚期，IκBα的消耗是转录和翻译水平调控的综合结果。泛素化和蛋白酶体降解对IκBα的分解均无明显作用。我们还证明，紫外线仅诱导p65（S276）的磷酸化，而肿瘤坏死因子-α诱导p65的Ser276和536位点的磷酸化。基于我们的结果，我们提出了一种新的机制，用于翻译调控的IκBα消耗和紫外线照射后24小时MSK介导的NF-κB激活。
