Lin K I, DiDonato J A, Hoffmann A, Hardwick J M, Ratan R R
Department of Molecular Microbiology and Immunology, The Johns Hopkins University School of Public Health, Baltimore, Maryland 21205, USA.
J Cell Biol. 1998 Jun 29;141(7):1479-87. doi: 10.1083/jcb.141.7.1479.
Recent studies have established cell type- specific, proapoptotic, or antiapoptotic functions for the transcription factor NF-kappaB. In each of these studies, inhibitors of NF-kappaB activity have been present before the apoptotic stimulus, and so the role of stimulus- induced NF-kappaB activation in enhancing or inhibiting survival could not be directly assessed. Sindbis virus, an alphavirus, induces NF-kappaB activation and apoptosis in cultured cell lines. To address whether Sindbis virus- induced NF-kappaB activation is required for apoptosis, we used a chimeric Sindbis virus that expresses a superrepressor of NF-kappaB activity. Complete suppression of virus-induced NF-kappaB activity neither prevents nor potentiates Sindbis virus-induced apoptosis. In contrast, inhibition of NF-kappaB activity before infection inhibits Sindbis virus-induced apoptosis. Our results demonstrate that suppression of steady-state, but not stimulus-induced NF-kappaB activity, regulates expression of gene products required for Sindbis virus-induced death. Furthermore, we show that in the same cell line, NF-kappaB can be proapoptotic or antiapoptotic depending on the death stimulus. We propose that the role of NF-kappaB in regulating apoptosis is determined by the death stimulus and by the timing of modulating NF-kappaB activity relative to the death stimulus.
最近的研究确定了转录因子NF-κB具有细胞类型特异性、促凋亡或抗凋亡功能。在这些研究中的每一项中，NF-κB活性抑制剂在凋亡刺激之前就已存在，因此刺激诱导的NF-κB激活在增强或抑制细胞存活中的作用无法直接评估。辛德毕斯病毒是一种甲病毒，可在培养的细胞系中诱导NF-κB激活和凋亡。为了研究辛德毕斯病毒诱导的NF-κB激活是否是凋亡所必需的，我们使用了一种表达NF-κB活性超抑制剂的嵌合辛德毕斯病毒。完全抑制病毒诱导的NF-κB活性既不能预防也不能增强辛德毕斯病毒诱导的凋亡。相反，在感染前抑制NF-κB活性可抑制辛德毕斯病毒诱导的凋亡。我们的结果表明，抑制稳态而非刺激诱导的NF-κB活性可调节辛德毕斯病毒诱导死亡所需的基因产物的表达。此外，我们表明在同一细胞系中，NF-κB根据死亡刺激的不同可能具有促凋亡或抗凋亡作用。我们提出，NF-κB在调节凋亡中的作用取决于死亡刺激以及相对于死亡刺激调节NF-κB活性的时间。
