DJ-1 restores p53 transcription activity inhibited by Topors/p53BP3.
DJ-1 restores p53 transcription activity inhibited by Topors/p53BP3.
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DOI：
10.3892/ijo.26.3.641
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发表时间：
2005-03
影响因子：
5.2
通讯作者：
Y. Shinbo;T. Taira;Takeshi Niki;Sanae M. M. Iguchi-Ariga-Sanae-M.-M.-Iguchi-Ariga-1395935820;H. Ariga
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文献类型：
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作者：
Y. Shinbo;T. Taira;Takeshi Niki;Sanae M. M. Iguchi-Ariga-Sanae-M.-M.-Iguchi-Ariga-1395935820;H. Ariga
DJ-1是一种多功能蛋白质，在转录调节和抗氧化应激中发挥作用，其功能的丧失被认为是导致帕金森氏症发病的原因。在此，我们报道了DJ-1在体外和体内都与Topors/p53BP3结合，Topors/p53BP3是一种与拓扑异构酶I和p53结合的环指蛋白，并且这两种蛋白在细胞中共存。随后发现DJ-1和P53在细胞中被Topors总和甲基化。研究还发现，DJ-1在体外和体内都与P53结合，紫外线照射细胞可刺激DJ-1与P53的共定位和结合。TOPORS抑制P53转录活性，DJ-1通过释放P53总甲基化恢复其转录活性，并呈剂量依赖性。这些发现表明，DJ-1通过Topors介导的SUMO化正向调节P53。
DJ-1 is a multi-functional protein that plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to result in onset of Parkinson's disease. Here, we report that DJ-1 bound to Topors/p53BP3, a ring finger protein binding to both topoisomerase I and p53, in vitro and in vivo and that both proteins were colocalized in cells. DJ-1 and p53 were then found to be sumoylated by Topors in cells. It was also found that DJ-1 bound to p53 in vitro and in vivo and that colocalization with and its binding to p53 were stimulated by UV irradiation of cells. Transcription activity of p53 was found to be abrogated by Topors concomitant with sumoylation of p53 in a dose-dependent manner, and DJ-1 restored its repressed activity by releasing the sumoylated form of p53. These findings suggest that DJ-1 positively regulates p53 through Topors-mediated sumoylation.