NGFI-13 Nuclear Orphan Receptor Nurr1 Interacts with p53 and Suppresses Its Transcriptional Activity
NGFI-13 Nuclear Orphan Receptor Nurr1 Interacts with p53 and Suppresses Its Transcriptional Activity
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NGFI-13 核孤儿受体 Nurr1 与 p53 相互作用并抑制其转录活性
DOI：
10.1158/1541-7786.mcr-08-0533
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发表时间：
2009-08-01
影响因子：
5.2
通讯作者：
Wang, Guanghui
中科院分区：
文献类型：
--
作者：
Zhang, Tao;Wang, Pingping;Wang, Guanghui
Nurr1是NGFI-B核孤儿受体家族的一员，该家族还包括另外两个成员Nur77和Nor-1。Nurr1对多巴胺能神经元的发育和存活至关重要。据报道，Nurr1具有抗凋亡功能，然而，Nurr1介导这些作用的机制尚不清楚。在这里，我们发现过表达Nurr1会降低Bax的表达，而敲低Nurr1会增加Bax的表达。Nurr1也与p53相互作用并抑制其组装。此外，Nurr1以相互作用依赖和剂量依赖的方式抑制p53的转录活性。此外，Nurr1保护细胞免受阿霉素诱导的细胞凋亡。这些发现证明Nurr1通过与p53相互作用和抑制p53促进细胞存活，从而暗示Nurr1可能在癌变和其他疾病中发挥重要作用。[j] .现代医学杂志，2009;7(8):1408-15。
Nurr1 is a member of the NGFI-B nuclear orphan receptor family which includes two other members, Nur77 and Nor-1. Nurr1 is essential for the development and survival of dopaminergic neurons. It was reported that Nurr1 has antiapoptotic functions, however, the mechanisms by which Nurr1 mediates these effects remain unknown. Here, we show that overexpression of Nurr1 decreases Bax expression whereas knockdown of Nurr1 increases Bax expression. Nurr1 also interacts with p53 and represses its assembly. Furthermore, Nurr1 represses p53 transcriptional activity in interaction-dependent and dose-dependent manners. Moreover, Nurr1 protects cells from doxorubicin-induced apoptosis. These findings provide evidence that Nurr1 promotes cell survival through its interacting with and repressing p53, thus implicating that Nurr1 may play an important role in carcinogenesis and other diseases. (Mol Cancer Res 2009;7(8):1408-15)