IFNalpha/beta promotes cell survival by activating NF-kappa B.
IFNalpha/beta promotes cell survival by activating NF-kappa B.
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DOI：
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发表时间：
2000
影响因子：
11.1
通讯作者：
C. Yang;A. Murti;S. Pfeffer;L. Basu;J. Kim;L. Pfeffer
中科院分区：
文献类型：
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作者：
C. Yang;A. Murti;S. Pfeffer;L. Basu;J. Kim;L. Pfeffer
干扰素通过信号转导和转录激活因子调节多种基因的表达，在宿主防御中发挥重要作用。我们发现，IFN α/β激活另一个重要的转录因子，NF-κ B。多种1型IFN诱导NF-κ B的DNA结合活性，并在不同的人、猴、大鼠和小鼠细胞组中通过IFN促进NF-κ B的DNA结合活性。人IFN促进表达1型IFN受体的人IFN α/β受体-1信号转导链的鼠细胞中的NF-κ B活化。IFN促进κ B α抑制剂（IkappaB α）丝氨酸磷酸化和降解，并刺激NF-κ B DNA结合和转录活性。重要的是，IFN通过保护细胞免受各种促凋亡刺激，如病毒感染和抗体介导的交联，促进细胞存活。IkappaB α的超阻遏形式的表达，除了抑制IFN介导的NF-κ B活化和IkappaB α降解外，还增强了IFN处理的细胞中的凋亡性细胞死亡。我们的结论是，通过IFN α/β激活NF-κ B整合到一个信号通路，通过IFN α/β受体-1链的1型IFN受体，促进细胞存活并置各种凋亡刺激。
IFNs play critical roles in host defense by modulating the expression of various genes via signal transducer and activator of transcription factors. We show that IFNalpha/beta activates another important transcription factor, NF-kappaB. DNA-binding activity of NF-kappaB was induced by multiple type 1 IFNs and was promoted by IFN in a diverse group of human, monkey, rat, and murine cells. Human IFN promoted NF-kappaB activation in murine cells that express the human IFNalpha/beta receptor-1 signal-transducing chain of the type 1 IFN receptor. IFN promotes inhibitor of kappa B alpha (IkappaBalpha) serine phosphorylation and degradation, and stimulates NF-kappaB DNA-binding and transcriptional activity. Importantly, IFN promotes cell survival by protecting cells against a variety of proapoptotic stimuli, such as virus infection and antibody-mediated crosslinking. Expression of superrepressor forms of IkappaBalpha, besides inhibiting IFN-mediated NF-kappaB activation and IkappaBalpha degradation, also enhanced apoptotic cell death in IFN-treated cells. We conclude that NF-kappaB activation by IFNalpha/beta is integrated into a signaling pathway through the IFNalpha/beta receptor-1 chain of the type 1 IFN receptor that promotes cell survival in apposition to various apoptotic stimuli.