Rajpal Arvind, Cho Yuri A, Yelent Biana, Koza-Taylor Petra H, Li Dongling, Chen Elaine, Whang Michael, Kang Chulho, Turi Thomas G, Winoto Astar
Department of Molecular and Cell Biology, Division of Immunology and Cancer Research Laboratory, 469 LSA, University of California, Berkeley, CA 94720-3200, USA.
EMBO J. 2003 Dec 15;22(24):6526-36. doi: 10.1093/emboj/cdg620.
Nur77 is a nuclear orphan steroid receptor that has been implicated in negative selection. Expression of Nur77 in thymocytes and cell lines leads to apoptosis through a mechanism that remains unclear. In some cell lines, Nur77 was reported to act through a transcription-independent mechanism involving translocation to mitochondria, leading to cytochrome c release. However, we show here that Nur77-mediated apoptosis in thymocytes does not involve cytoplasmic cytochrome c release and cannot be rescued by Bcl-2. Microarray analysis shows that Nur77 induces many genes, including two novel genes (NDG1, NDG2) and known apoptotic genes FasL and TRAIL. Characterization of NDG1 and NDG2 indicates that NDG1 initiates a novel apoptotic pathway in a Bcl-2-independent manner. Thus Nur77-mediated apoptosis in T cells involves Bcl-2 independent transcriptional activation of several known and novel apoptotic pathways.
Nur77是一种核孤儿类固醇受体,与阴性选择有关。Nur77在胸腺细胞和细胞系中的表达通过一种尚不清楚的机制导致细胞凋亡。在一些细胞系中,据报道Nur77通过一种不依赖转录的机制发挥作用,该机制涉及转位至线粒体,导致细胞色素c释放。然而,我们在此表明,Nur77介导的胸腺细胞凋亡不涉及细胞质细胞色素c释放,且不能被Bcl-2挽救。微阵列分析表明,Nur77诱导许多基因,包括两个新基因(NDG1、NDG2)以及已知的凋亡基因FasL和TRAIL。对NDG1和NDG2的特性分析表明,NDG1以不依赖Bcl-2的方式启动一条新的凋亡途径。因此,Nur77介导的T细胞凋亡涉及几种已知和新的凋亡途径的不依赖Bcl-2的转录激活。