Constitutive rat multidrug-resistance protein 2 gene transcription is down-regulated by Y-box protein 1

Biochem Biophys Res Commun. 2003 Sep 26;309(3):612-8. doi: 10.1016/j.bbrc.2003.08.041.


Background/aims: Molecular mechanisms underlying transcriptional rat multidrug-resistance protein 2 (Mrp2, Abcc2) gene regulation are mostly unclear. Given the presence of putative binding sites for the Y-box binding protein YB-1 in the regulatory sequence, its trans-regulatory influence was analyzed.

Methods: Reporter assays in HepG2 cells with various Mrp2 deletion constructs in the absence and presence of co-transfected YB-1 were performed. DNA binding studies with recombinant YB-1 protein and nuclear extracts obtained from HepG2 cells and rat liver tissue were carried out.

Results: The minimal promoter sequence was confined to the proximal 186 bp. A YB-1 responsive element, Mrp2 YRE-1, was mapped at -186/-157, which exhibits specific YB-1 binding. YB-1 acts as a potent repressor of Mrp2 promoter activity in vitro.

Conclusions: Constitutive Mrp2 gene expression is conferred through the proximal -186 bp. YB-1 acts as a repressor in vitro by specific binding to a defined element in the proximal promoter sequence.

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Animals
  • Base Sequence
  • Binding Sites
  • CCAAT-Enhancer-Binding Proteins / metabolism*
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • DNA-Binding Proteins*
  • Down-Regulation*
  • Male
  • Molecular Sequence Data
  • NFI Transcription Factors
  • Promoter Regions, Genetic
  • Rats
  • Rats, Sprague-Dawley
  • Regulatory Sequences, Nucleic Acid
  • Repressor Proteins / metabolism*
  • Response Elements
  • Sequence Homology, Nucleic Acid
  • Transcription Factors*
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Y-Box-Binding Protein 1


  • ATP-Binding Cassette Transporters
  • Abcc2 protein, rat
  • CCAAT-Enhancer-Binding Proteins
  • Carrier Proteins
  • DNA-Binding Proteins
  • NFI Transcription Factors
  • Repressor Proteins
  • Transcription Factors
  • Y-Box-Binding Protein 1
  • Ybx1 protein, rat