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

A Geier1, P R Mertens, T Gerloff

  • 1Department of Internal Medicine III, University Hospital, Aachen, Germany.

Biochemical and Biophysical Research Communications
|September 10, 2003
PubMed
Abstract

Insights

The Y-box binding protein YB-1 represses rat multidrug-resistance protein 2 (Mrp2, Abcc2) gene expression by binding to a specific promoter element. This finding clarifies a key mechanism in Mrp2 gene regulation.

Area of Science:

  • Molecular biology
  • Gene regulation
  • Drug metabolism

Background:

  • The transcriptional regulation of the rat multidrug-resistance protein 2 (Mrp2, Abcc2) gene is not fully understood.
  • The Mrp2 gene is crucial for drug transport and detoxification.

Purpose of the Study:

  • To investigate the role of the Y-box binding protein YB-1 in the transcriptional regulation of the rat Mrp2 gene.
  • To identify potential YB-1 binding sites within the Mrp2 gene promoter.

Main Methods:

  • Reporter gene assays were conducted in HepG2 cells using various Mrp2 promoter deletion constructs.
  • DNA binding studies were performed using recombinant YB-1 protein and nuclear extracts from HepG2 cells and rat liver.

Main Results:

  • The minimal promoter region for the rat Mrp2 gene was identified as the proximal 186 bp.
  • A YB-1 responsive element (Mrp2 YRE-1) was mapped to the -186/-157 region of the promoter.
  • YB-1 was found to bind specifically to the Mrp2 YRE-1 element and act as a repressor of Mrp2 promoter activity in vitro.

Conclusions:

  • Constitutive expression of the Mrp2 gene is regulated by its proximal -186 bp promoter sequence.
  • YB-1 functions as a repressor of Mrp2 gene transcription through specific binding to the identified promoter element.

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