NF-κB antiapoptosis:: Induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation
NF-κB antiapoptosis:: Induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation
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DOI：
10.1126/science.281.5383.1680
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发表时间：
1998-09-11
期刊：
影响因子：
56.9
通讯作者：
Baldwin, AS
中科院分区：
文献类型：
--
作者：
Wang, CY;Mayo, MW;Baldwin, AS
肿瘤坏死因子 α (TNF-α) 与 TNF 受体 (TNFR) 结合可能会引发细胞凋亡并激活转录因子核因子 kappa B (NF-kappa B)，后者通过未知机制抑制细胞凋亡。 NF-kappa B 的激活被发现可以阻断 caspase-8 的激活。 TRAF1（TNFR 相关因子 1）、TRAF2 以及凋亡抑制剂 (IAP) 蛋白 c-IAP1 和 c-IAP2 被确定为 NF-kappa B 转录活性的基因靶标。在 NF-κ B 失活的细胞中，所有这些蛋白质都需要完全抑制 TNF 诱导的细胞凋亡，而 c-IAP1 和 c-IAP2 足以抑制依托泊苷诱导的细胞凋亡。因此，NF-κ B 激活一组基因产物，这些基因产物在最早的检查点协同发挥作用，抑制 TNF-α 介导的细胞凋亡，并在更远端发挥作用，抑制基因毒剂介导的细胞凋亡。
Tumor necrosis factor alpha (TNF-alpha) binding to the TNF receptor (TNFR) potentially initiates apoptosis and activates the transcription factor nuclear factor kappa B (NF-kappa B), which suppresses apoptosis by an unknown mechanism. The activation of NF-kappa B was found to block the activation of caspase-8. TRAF1 (TNFR-associated factor 1), TRAF2, and the inhibitor-of-apoptosis (IAP) proteins c-IAP1 and c-IAP2 were identified as gene targets of NF-kappa B transcriptional activity. in cells in which NF-kappa B was inactive, all of these proteins were required to fully suppress TNF-induced apoptosis, whereas c-IAP1 and c-IAP2 were sufficient to suppress etoposide-induced apoptosis. Thus, NF-kappa B activates a group of gene products that function cooperatively at the earliest checkpoint to suppress TNF-alpha-mediated apoptosis and that function more distally to suppress genotoxic agent-mediated apoptosis.