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Suppression of steady-state, but not stimulus-induced NF-kappaB activity inhibits alphavirus-induced apoptosis.
J Cell Biol. 1998 Jun 29; 141(7):1479-87.JC

Abstract

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.

Authors+Show Affiliations

Department of Molecular Microbiology and Immunology, The Johns Hopkins University School of Public Health, Baltimore, Maryland 21205, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9647642

Citation

Lin, K I., et al. "Suppression of Steady-state, but Not Stimulus-induced NF-kappaB Activity Inhibits Alphavirus-induced Apoptosis." The Journal of Cell Biology, vol. 141, no. 7, 1998, pp. 1479-87.
Lin KI, DiDonato JA, Hoffmann A, et al. Suppression of steady-state, but not stimulus-induced NF-kappaB activity inhibits alphavirus-induced apoptosis. J Cell Biol. 1998;141(7):1479-87.
Lin, K. I., DiDonato, J. A., Hoffmann, A., Hardwick, J. M., & Ratan, R. R. (1998). Suppression of steady-state, but not stimulus-induced NF-kappaB activity inhibits alphavirus-induced apoptosis. The Journal of Cell Biology, 141(7), 1479-87.
Lin KI, et al. Suppression of Steady-state, but Not Stimulus-induced NF-kappaB Activity Inhibits Alphavirus-induced Apoptosis. J Cell Biol. 1998 Jun 29;141(7):1479-87. PubMed PMID: 9647642.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suppression of steady-state, but not stimulus-induced NF-kappaB activity inhibits alphavirus-induced apoptosis. AU - Lin,K I, AU - DiDonato,J A, AU - Hoffmann,A, AU - Hardwick,J M, AU - Ratan,R R, PY - 1998/7/1/pubmed PY - 1998/7/1/medline PY - 1998/7/1/entrez SP - 1479 EP - 87 JF - The Journal of cell biology JO - J Cell Biol VL - 141 IS - 7 N2 - 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. SN - 0021-9525 UR - https://www.unboundmedicine.com/medline/citation/9647642/Suppression_of_steady_state_but_not_stimulus_induced_NF_kappaB_activity_inhibits_alphavirus_induced_apoptosis_ L2 - https://rupress.org/jcb/article-lookup/doi/10.1083/jcb.141.7.1479 DB - PRIME DP - Unbound Medicine ER -