文章基本信息

标题：NF-κB-mediated up-regulation of Bcl-x and Bfl-1/A1 is required for CD40 survival signaling in B lymphocytes
本地全文：下载
作者：Ho H. Lee ; Hajir Dadgostar ; Qingwen Cheng 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：16
页码：9136-9141
DOI：10.1073/pnas.96.16.9136
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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-{kappa}B pathway by overexpression of a dominant-active inhibitor of NF-{kappa}B 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-{kappa}B-binding sequence was found to support NF-{kappa}B-dependent transcriptional activation. Furthermore, expression of physiological levels of Bcl-x protected B cells from Fas-mediated apoptosis in the absence of NF-{kappa}B signaling. Thus, our results suggest that CD40-mediated cell survival proceeds through NF-{kappa}B-dependent up-regulation of Bcl-2 family members.