de Léséleuc L, Denis F
1INRS-Institut Armand-Frappier, Laval, QC, Canada.
Cell Death Differ. 2006 Feb;13(2):293-300. doi: 10.1038/sj.cdd.4401737.
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-kappaB activity, and DNA-binding inhibitors confirmed the contribution of NF-kappaB to Nur77 antiapoptotic activity. Nur77 overexpression leads to NF-kappaB-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.
孤儿核受体Nur77被认为是细胞凋亡的介质，也与生长促进和凋亡抗性有关。本研究旨在评估Nur77对不同凋亡刺激的作用。在成纤维细胞系HEK293中过表达Nur77可增强对死亡受体激活、DNA损伤剂和内质网应激诱导的程序性细胞死亡的抗性。Nur77过表达导致NF-κB活性增强，DNA结合抑制剂证实NF-κB对Nur77抗凋亡活性有作用。Nur77过表达导致抗凋亡基因cIAP1的NF-κB依赖性诱导。矛盾的是，虽然显性负性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诱导的凋亡。这些结果表明，Nur77与其他转录因子之间的核相互作用有助于细胞对不同凋亡诱导剂的命运决定。
