REDD1, a developmentally regulated transcriptional target of p63 and p53, links p63 to regulation of reactive oxygen species
REDD1, a developmentally regulated transcriptional target of p63 and p53, links p63 to regulation of reactive oxygen species
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DOI：
10.1016/s1097-2765(02)00706-2
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发表时间：
2002-11-01
期刊：
影响因子：
16
通讯作者：
Haber, DA
中科院分区：
文献类型：
--
作者：
Ellisen, LW;Ramsayer, KD;Haber, DA
我们将 REDD1 确定为 DNA 损伤后诱导的 p53 的新转录靶标。在胚胎发生过程中，REDD1 表达反映了 p53 家族成员 p63 的组织特异性模式，TP63 缺失胚胎实际上没有显示 REDDI 表达，而在 p63 表达后，REDDI 在小鼠胚胎成纤维细胞中恢复。在分化初级角质形成细胞时，TP63 和 REDD1 表达协同下调，并且任一基因的异位表达都会抑制体外分化。 REDD1 似乎在调节活性氧 (ROS) 中发挥作用；我们发现，TP63 缺失的成纤维细胞的 ROS 水平降低，对氧化应激的敏感性降低，而在 TP63 或 REDD1 异位表达后，这些水平都会增加。因此，REDD1 编码一个共享的转录目标，该目标在 p53 依赖性 DNA 损伤反应和 p63 介导的上皮分化调节中涉及 ROS。
We identified REDD1 as a novel transcriptional target of p53 induced following DNA damage. During embryogenesis, REDD1 expression mirrors the tissuespecific pattern of the p53 family member p63, and TP63 null embryos show virtually no expression of REDDI, which is restored in mouse embryo fibroblasts following p63 expression. In differentiating primary keratinocytes, TP63 and REDD1 expression are coordinately downregulated, and ectopic expression of either gene inhibits in vitro differentiation. REDD1 appears to function in the regulation of reactive oxygen species (ROS); we show that TP63 null fibroblasts have decreased ROS levels and reduced sensitivity to oxidative stress, which are both increased following ectopic expression of either TP63 or REDD1. Thus, REDD1 encodes a shared transcriptional target that implicates ROS in the p53-dependent DNA damage response and in p63-mediated regulation of epithelial differentiation.