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Title	en Transcriptional Activation of Low-Density Lipoprotein Receptor Gene by DJ-1 and Effect of DJ-1 on Cholesterol Homeostasis
Creator	en Yamaguchi, Shiori en Yamane, Takuya en Takahashi-Niki, Kazuko NRID 1000050447645 en Kato, Izumi en Niki, Takeshi NRID 1000090377193 en Goldberg, Matthew S. en Shen, Jie en Ishimoto, Kenji en Doi, Takefumi NRID 1000000211409 en Iguchi-Ariga, Sanae M. M. NRID 1000090184283 en Ariga, Hiroyoshi NRID 1000020143505
Accessrights	open access
Rights	http://creativecommons.org/licenses/by/3.0/ en Creative Commons Attribution 3.0 Unported
Subject	NDC 493
Description	Abstract en DJ-1 is a novel oncogene and also causative gene for familial Parkinson's disease park7. DJ-1 has multiple functions that include transcriptional regulation, anti-oxidative reaction and chaperone and mitochondrial regulation. For 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 the low-density lipoprotein receptor (LDLR) gene is a transcriptional target gene for DJ-1. Reduced expression of LDLR mRNA and protein was observed in DJ-1-knockdown cells and DJ-1-knockout mice and this occurred at the transcription level. Reporter gene assays using various deletion and point mutations of the LDLR promoter showed that DJ-1 stimulated promoter activity by binding to the sterol regulatory element (SRE) with sterol regulatory element binding protein (SREBP) and that stimulating activity of DJ-1 toward LDLR promoter activity was enhanced by oxidation of DJ-1. Chromatin immunoprecipitation, gel-mobility shift and co-immunoprecipitation assays showed that DJ-1 made a complex with SREBP on the SRE. Furthermore, it was found that serum LDL cholesterol level was increased in DJ-1-knockout male, but not female, mice and that the increased serum LDL cholesterol level in DJ-1-knockout male mice was cancelled by administration with estrogen, suggesting that estrogen compensates the increased level of serum LDL cholesterol in DJ-1-knockout female mice. This is the first report that DJ-1 participates in metabolism of fatty acid synthesis through transcriptional regulation of the LDLR gene.
Publisher	en Public Library of Science
Date	Issued2012-05-30
Language	eng
Resource Type	journal article
Version Type	VoR
Identifier	HDL http://hdl.handle.net/2115/49574
Relation	isIdenticalTo DOI https://doi.org/10.1371/journal.pone.0038144
Journal	PISSN 1932-6203 en PLoS One Volume Number7 Issue Number5 Page Starte38144
File	fulltext PLoSOne7-5_e38144.pdf 2.02 MB (application/pdf) Issued2012-05-30
Oaidate	2023-07-26