Suppression of Steady-state, but not Stimulus-induced NF-κB Activity Inhibits Alphavirus-induced Apoptosis
Open Access
- 29 June 1998
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 141 (7), 1479-1487
- https://doi.org/10.1083/jcb.141.7.1479
Abstract
Recent studies have established cell type– specific, proapoptotic, or antiapoptotic functions for the transcription factor NF-κB. In each of these studies, inhibitors of NF-κB activity have been present before the apoptotic stimulus, and so the role of stimulus- induced NF-κB activation in enhancing or inhibiting survival could not be directly assessed. Sindbis virus, an alphavirus, induces NF-κB activation and apoptosis in cultured cell lines. To address whether Sindbis virus– induced NF-κB activation is required for apoptosis, we used a chimeric Sindbis virus that expresses a superrepressor of NF-κB activity. Complete suppression of virus-induced NF-κB activity neither prevents nor potentiates Sindbis virus–induced apoptosis. In contrast, inhibition of NF-κB activity before infection inhibits Sindbis virus–induced apoptosis. Our results demonstrate that suppression of steady-state, but not stimulus-induced NF-κB activity, regulates expression of gene products required for Sindbis virus–induced death. Furthermore, we show that in the same cell line, NF-κB can be proapoptotic or antiapoptotic depending on the death stimulus. We propose that the role of NF-κB in regulating apoptosis is determined by the death stimulus and by the timing of modulating NF-κB activity relative to the death stimulus.Keywords
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