RRC ID 19249
Author Ishikawa S, Taira T, Takahashi-Niki K, Niki T, Ariga H, Iguchi-Ariga SM.
Title Human DJ-1-specific transcriptional activation of tyrosine hydroxylase gene.
Journal J Biol Chem
Abstract Loss-of-function mutation in the DJ-1 gene causes a subset of familial Parkinson disease. The mechanism underlying DJ-1-related selective vulnerability in the dopaminergic pathway is, however, not known. DJ-1 has multiple functions, including transcriptional regulation, and one of transcriptional target genes for DJ-1 is the tyrosine hydroxylase (TH) gene, the product of which is a key enzyme for dopamine biosynthesis. It has been reported that DJ-1 is a neuroprotective transcriptional co-activator that sequesters a transcriptional co-repressor polypyrimidine tract-binding protein-associated splicing factor (PSF) from the TH gene promoter. In this study, we found that knockdown of human DJ-1 by small interference RNA in human dopaminergic cell lines attenuated TH gene expression and 4-dihydroxy-L-phenylalanine production but that knockdown or knock-out of mouse DJ-1 in mouse cell lines or in mice did not affect such expression and TH activity. In reporter assays using the human TH gene promoter linked to the luciferase gene, stimulation of TH promoter activity was observed in human cells, but not mouse cells, that had been transfected with DJ-1. Although human DJ-1 and mouse DJ-1 were associated either with human or with mouse PSF, TH promoter activity inhibited by PSF was restored by human DJ-1 but not by mouse DJ-1. Chromatin immunoprecipitation assays revealed that the complex of PSF with DJ-1 bound to the human but not the mouse TH gene promoter. These results suggest a novel species-specific transcriptional regulation of the TH promoter by DJ-1 and one of the mechanisms for no reduction of TH in DJ-1-knock-out mice.
Volume 285(51)
Pages 39718-31
Published 2010-12-17
DOI 10.1074/jbc.M110.137034
PII S0021-9258(20)60502-6
PMID 20938049
PMC PMC3000953
MeSH Animals Cell Line Dopamine / biosynthesis Dopamine / genetics Gene Expression Regulation, Enzymologic / physiology* Gene Knockdown Techniques Humans Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* Levodopa / genetics Levodopa / metabolism Mice Mice, Knockout Oncogene Proteins / genetics Oncogene Proteins / metabolism* Parkinson Disease / genetics Parkinson Disease / metabolism Peroxiredoxins Protein Deglycase DJ-1 RNA, Small Interfering / genetics Response Elements / physiology* Transcriptional Activation / physiology* Tyrosine 3-Monooxygenase / biosynthesis* Tyrosine 3-Monooxygenase / genetics
IF 4.238
Times Cited 50
Human and Animal Cells SK-N-SH(RCB0426)