期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 280, 期 23, 页码 22287-22296出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M410923200
关键词
-
The activation of the transcription factor nuclear factor-kappa B (NF-kappa B) by growth factors, cytokines, and cellular stress can prevent apoptosis, but the underlying mechanism is unknown. Here we provide evidence for an action of NF-kappa B on calcium signaling that accounts for its anti-apoptotic function. Embryonic fibroblasts lacking the transactivating subunit of NF-kappa B RelA (p65) exhibit enhanced inositol 1,4,5- trisphosphate (IP3) receptor-mediated calcium release and increased sensitivity to apoptosis, which are restored upon re-expression of RelA. The size of the endoplasmic reticulum (ER) calcium pool and the number of IP3 receptors per cell are decreased in response to stimuli that activate NF-kappa B and are increased when NF-kappa B activity is suppressed. The selective antagonism of IP3 receptors blocks apoptosis in RelA-deficient cells, whereas activation of NF-kappa B in normal cells leads to decreased levels of the type 1 IP3 receptor and decreased calcium release. Overexpression of Bcl-2 normalizes ER calcium homeostasis and prevents calcium-mediated apoptosis in RelA-deficient cells. These findings establish an ER calcium channel as a pivotal target for NF-kappa B-mediated cell survival signaling.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据