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Title
  • Transcriptional Activation of Low-Density Lipoprotein Receptor Gene by DJ-1 and Effect of DJ-1 on Cholesterol Homeostasis
Creator

Yamaguchi, Shiori

Yamane, Takuya

Takahashi-Niki, Kazuko

Kato, Izumi

Niki, Takeshi

Goldberg, Matthew S.

Shen, Jie

Ishimoto, Kenji

Doi, Takefumi

Iguchi-Ariga, Sanae M. M.

Ariga, Hiroyoshi

Rights
    • http://creativecommons.org/licenses/by/3.0/
Subject
  • NDC 493
Description
Other
  • 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.
PublisherPublic Library of Science
Date Issued 2012-05-30
Languageeng
NIItypejournal article
VersiontypeVoR
Identifier URI http://hdl.handle.net/2115/49574
Relation
  • isIdenticalTo DOI https://doi.org/10.1371/journal.pone.0038144
Journal
    • ISSN 1932-6203
    • PLoS One
    7(5), e38144
File
Oaidate2017-10-15T15:00:00Z