Transcriptional activation of the cholecystokinin gene by DJ-1 through interaction of DJ-1 with RREB1 and the effect of DJ-1 on the cholecystokinin level in mice.

Transcriptional activation of the cholecystokinin gene by DJ-1 through interaction of DJ-1 with RREB1 and the effect of DJ-1 on the cholecystokinin level in mice.
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DOI:
10.1371/journal.pone.0078374
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Ariga H
Ariga H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yamane T;Suzui S;Kitaura H;Takahashi-Niki K;Iguchi-Ariga SM;Ariga H

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DJ-1是一种癌基因,也是家族性帕金森病的致病基因。DJ-1具有多种功能,包括转录调控。DJ-1作为共激活因子与多种转录因子结合,刺激或抑制靶基因的表达。在本研究中,我们发现CCK基因是DJ-1的转录靶基因。CCK是一种多肽激素,具有收缩胆囊壁和促进胰液分泌的作用。CCK与多巴胺共同定位于黑质,调节多巴胺的释放。在DJ-1基因敲除细胞中,CCK mRNA的表达降低。Ras反应元件(RRE)和Sp1位点是启动子活性所必需的,DJ-1通过与RRE结合蛋白1(RREBP1)结合来刺激启动子活性。DJ-1与RREB1结合,但不与Sp1结合。此外,还观察到DJ-1基因敲除小鼠的血清CCK水平低于野生型小鼠。这是第一个显示DJ-1参与多肽激素合成的报道。
DJ-1 is an oncogene and also causative gene for familial Parkinson’s disease. DJ-1 has multiple functions, including transcriptional regulation. DJ-1 acts as a coactivator that binds to various transcription factors, resulting in stimulation or repression of the expression of their target genes. In this study, we found that the cholecystokinin (CCK) gene is a transcriptional target gene for DJ-1. CCK is a peptide hormone and plays roles in contraction of the gallbladder and in promotion of secretion of pancreatic fluid. CCK is co-localized with dopamine in the substantia nigra to regulate release of dopamine. Reduced expression of CCK mRNA was observed in DJ-1-knockdown cells. The Ras-responsive element (RRE) and Sp1 site were essential for promoter activity, and DJ-1 stimulated promoter activity by binding to RRE-binding protein 1 (RREBP1). The complex of DJ-1 with RREB1 but not with Sp1 bound to the RRE. Furthermore, the reduced CCK level in the serum from DJ-1-knockout mice compared to that from wild-type mice was observed. This is the first report showing that DJ-1 participates in peptide hormone synthesis.
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