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NF-κB-mediated up-regulation of Bcl-x and Bfl-1/A1 is required for CD40 survival signaling in B lymphocytes
Open accessAbstract
Activation of CD40 is essential for thymus-dependent humoral immune responses and rescuing B cells from apoptosis. Many of the effects of CD40 are believed to be achieved through altered gene expression. In addition to Bcl-x, a known CD40-regulated antiapoptotic molecule, we identified a related antiapoptotic molecule, A1/Bfl-1, as a CD40-inducible gene. Inhibition of the NF-κB pathway by overexpression of a dominant-active inhibitor of NF-κB abolished CD40-induced up-regulation of both the Bfl-1 and Bcl-x genes and also eliminated the ability of CD40 to rescue Fas-induced cell death. Within the upstream promoter region of Bcl-x, a potential NF-κB-binding sequence was found to support NF-κB-dependent transcriptional activation. Furthermore, expression of physiological levels of Bcl-x protected B cells from Fas-mediated apoptosis in the absence of NF-κB signaling. Thus, our results suggest that CD40-mediated cell survival proceeds through NF-κB-dependent up-regulation of Bcl-2 family members.
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Krikos, A., Laherty, C. D., & Dixit, V. M. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)37138-8 · Cited by 444
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Metadata
- Authors
- Lee, H. H., Dadgostar, H., Cheng, Q., Shu, J., & Cheng, G.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1999-08-03
- Volume
- 96
- Issue
- 16
- Pages
- 9136-9141
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2015788325
- Cited by
- 521
- References
- 1
- FWCI
- 18.40
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: NF-κB-mediated up-regulation of Bcl-x and Bfl-1/A1 is required for CD40 survival signaling in B lymphocytes. https://app.cochat.ai/papers/10.1073/pnas.96.16.9136
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- Lee, H. H., Dadgostar, H., Cheng, Q., Shu, J., & Cheng, G. (1999). NF-κB-mediated up-regulation of Bcl-x and Bfl-1/A1 is required for CD40 survival signaling in B lymphocytes. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.96.16.9136
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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