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NF-kappa B is required for cell death induction by latent membrane protein 1 of Epstein-Barr virus

机译:EB病毒潜伏膜蛋白1诱导细胞死亡需要NF-κB

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摘要

NF-kappaB is a transcription factor known to promote or antagonize cell death depending on cell types and stimuli. Here, we demonstrate that expression of latent membrane protein 1 (LMP1), an Epstein-Barr virus (EBV)-encoded membrane protein, triggers programmed cell death in an NF-kappaB-dependent manner. Co-expression of NF-kappaB inhibitors completely prevented activation of NF-kappaB and LMP1-induced cell death. Addition therein of RelA, an active subunit of NF-kappaB, restored the NF-kappaB activation and cell death induction by LMP1, but RelA alone did not induce cell death. These results indicate that the activation of NF-kappaB is required for cell death induced by LMP1. Moreover, LMP1 induced activation of caspase-3 via the activation of NF-kappaB. Studies with z-VAD-fmk, a caspase inhibitor, indicated that NF-kappaB mediated both caspase-dependent and -independent death pathways. In conclusion, the cell death induced by LMP1 uncovered caspase-dependent and -independent death pathways both of which require NF-kappaB. (C) 2002 Elsevier Science Inc. All rights reserved. [References: 55]
机译:NF-κB是一种转录因子,已知可根据细胞类型和刺激来促进或拮抗细胞死亡。在这里,我们证明潜伏膜蛋白1(LMP1),一种爱泼斯坦-巴尔病毒(EBV)编码的膜蛋白的表达,以NF-κB依赖性的方式触发程序性细胞死亡。 NF-kappaB抑制剂的共表达完全阻止了NF-kappaB的激活和LMP1诱导的细胞死亡。在其中添加RelA,其为NF-κB的活性亚基,恢复了LMP1对NF-kappaB的活化和细胞死亡诱导,但是单独的RelA并没有诱导细胞死亡。这些结果表明,NF-κB的激活是LMP1诱导的细胞死亡所必需的。此外,LMP1通过激活NF-κB诱导了caspase-3的激活。用半胱天冬酶抑制剂z-VAD-fmk进行的研究表明,NF-κB介导了半胱天冬酶依赖性和非依赖性死亡途径。总之,由LMP1诱导的细胞死亡揭示了caspase依赖性和非依赖性死亡途径,两者均需要NF-κB。 (C)2002 Elsevier Science Inc.保留所有权利。 [参考:55]

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