TR4 orphan nuclear receptor functions as an apoptosis modulator via regulation of Bcl-2 gene expression
TR4 orphan nuclear receptor functions as an apoptosis modulator via regulation of Bcl-2 gene expression
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DOI：
10.1016/j.bbrc.2007.06.168
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发表时间：
2007-09-21
影响因子：
3.1
通讯作者：
Chang, Chawnshang
中科院分区：
文献类型：
--
作者：
Kim, Eungseok;Ma, Wen-Lung;Chang, Chawnshang
虽然Bcl2在细胞凋亡中发挥重要作用，但其与孤儿核受体的关系尚不清楚。在此，我们报道了从TR4基因缺陷(TR4(-/-))小鼠制备的小鼠胚胎成纤维细胞(MEF)比TR4-野生型(TR4(+/+))小鼠更容易受到紫外线辐射诱导的凋亡。紫外线照射可显著增加TR4(-/-)MEF的凋亡率，其机制可能与下调Bcl2RNA和蛋白表达，提高caspase-3活性有关。此外，与雄激素受体(AR)和受体相互作用蛋白140(RIP140)等TR4共调控因子共转染可剂量依赖性地抑制TR4诱导的Bcl2基因表达。综上所述，我们的结果表明，TR4可能通过诱导Bcl2基因的表达而发挥细胞凋亡的调节作用。(C)2007 Elsevier Inc.保留所有权利。
While Bcl-2 plays an important role in cell apoptosis, its relationship to the orphan nuclear receptors remains unclear. Here we report that mouse embryonic fibroblast (MEF) cells prepared from TR4-deficient (TR4(-/-)) mice are more susceptible to UV-irradiation mediated apoptosis compared to TR4-Wildtype (TR4(+/+)) littermates. Substantial increasing TR4(-/-) MEF apoptosis to UV-irradiation was correlated to the down-regulation of Bcl-2 RNA and protein expression and collaterally increased caspase-3 activity. Furthermore, this TR4-induced Bcl-2 gene expression can be suppressed by co-transfection with TR4 coregulators, such as androgen receptor (AR) and receptor-interacting protein 140 (RIP140) in a dose-dependent manner. Together, our results demonstrate that TR4 might function as an apoptosis modulator through induction of Bcl-2 gene expression. (c) 2007 Elsevier Inc. All rights reserved.