Stein Susanne, Thomas Emily K, Herzog Birger, Westfall Matthew D, Rocheleau Jonathan V, Jackson Roger S, Wang Mai, Liang Peng
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
J Biol Chem. 2004 Nov 19;279(47):48930-40. doi: 10.1074/jbc.M400386200. Epub 2004 Sep 17.
Although a number of target genes for the tumor suppressor p53 have been described, the mechanism of p53-dependent apoptosis is incompletely understood. Thus, it is essential to identify and characterize additional target genes that could mediate apoptosis. In the study reported here, we isolated a p53-regulated gene named NDRG1 (N-Myc down-regulated gene 1). Its expression is induced by DNA damage in a p53-dependent fashion. The promoter region of the NDRG1 gene contains a p53 binding site that confers p53-dependent transcriptional activation via a heterologous reporter. RNA interference and inducible gene expression approaches suggest that NDRG1 is necessary but not sufficient for p53-mediated caspase activation and apoptosis. This report further supports the notion that p53 controls a network of genes that are required for its apoptotic function.
尽管已经描述了许多肿瘤抑制因子p53的靶基因,但p53依赖的细胞凋亡机制仍未完全阐明。因此,识别和鉴定可能介导细胞凋亡的其他靶基因至关重要。在本文报道的研究中,我们分离出一个名为NDRG1(N-Myc下调基因1)的p53调控基因。其表达以p53依赖的方式被DNA损伤诱导。NDRG1基因的启动子区域包含一个p53结合位点,该位点通过异源报告基因赋予p53依赖的转录激活。RNA干扰和诱导基因表达方法表明,NDRG1对于p53介导的半胱天冬酶激活和细胞凋亡是必要的,但并不充分。本报告进一步支持了p53控制其凋亡功能所需的基因网络这一观点。