Inhibition of apoptosis by Nur77 through NF-κB activity modulation
Inhibition of apoptosis by Nur77 through NF-κB activity modulation
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DOI：
10.1038/sj.cdd.4401737
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发表时间：
2006-02-01
影响因子：
12.4
通讯作者：
Denis, F
中科院分区：
文献类型：
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作者：
de Léséleuc, L;Denis, F
孤儿核受体 Nur77 被描述为细胞凋亡的介质，并且还与生长促进和细胞凋亡抗性相关。本研究旨在评估 Nur77 对不同细胞凋亡刺激的贡献。 Nur77 在成纤维细胞系 HEK293 中的过度表达促进了对由死亡受体结合、DNA 损伤剂和内质网应激诱导的程序性细胞死亡的抵抗。 Nur77 过表达导致 NF-kappa B 活性增强，DNA 结合抑制剂证实了 NF-kappa B 对 Nur77 抗凋亡活性的贡献。 Nur77 过表达导致抗凋亡基因 cIAP1 的 NF-kappa B 依赖性诱导。矛盾的是，虽然显性失活的 Nur77 表达使细胞对 Fas 配体诱导的细胞死亡敏感，但它以类似于野生型 Nur77 的方式保护细胞免受内质网应激凋亡。这些结果表明，Nur77 和其他转录因子之间的核串扰有助于响应不同凋亡诱导剂的细胞命运。
The orphan nuclear receptor Nur77 has been described as a mediator of apoptosis and has also been associated with growth promotion and apoptotic resistance. This study aimed at evaluating the contribution of Nur77 to different apoptotic stimuli. Nur77 overexpression in the fibroblastic cell line HEK293 promoted resistance to programmed cell death induced by death receptor engagement, DNA-damaging agents and endoplasmic reticulum stress. Nur77 overexpression led to enhanced NF-kappa B activity, and DNA-binding inhibitors confirmed the contribution of NF-kappa B to Nur77 antiapoptotic activity. Nur77 overexpression leads to NF-kappa B-dependent induction of the antiapoptotic gene cIAP1. Paradoxically, while dominant-negative Nur77 expression sensitised cells to Fas ligand-induced cell death, it protected cells from endoplasmic reticulum stress apoptosis in a manner similar to wild-type Nur77. These results show that nuclear crosstalk between Nur77 and other transcription factors contribute to cell fate in response to different apoptosis-inducing agents.