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

PLoS One. 2013 Nov 5;8(11):e78374. doi: 10.1371/journal.pone.0078374. eCollection 2013.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholecystokinin / genetics
  • Cholecystokinin / metabolism*
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Mice
  • Mice, Knockout
  • NIH 3T3 Cells
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Peroxiredoxins
  • Protein Deglycase DJ-1
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNA-Binding Proteins
  • Oncogene Proteins
  • Cholecystokinin
  • Peroxiredoxins
  • PARK7 protein, mouse
  • Protein Deglycase DJ-1

Grants and funding

This work was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) and by the Program for Promotion of Fundamental Studies in Health Science of the National Institute of Biomedical Innovation (NIBIO) in Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.