Transcriptional control of the human aldehyde dehydrogenase 2 promoter by hepatocyte nuclear factor 4: Inhibition by cyclic AMP and COUP transcription factors

Min You, Monika Fischer, David Crabb, Kyoo Cho Won

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

An important regulatory element (designated FP330-3′) of the ALDH2 promoter mediates activation by hepatocyte nuclear factor 4 (HNF4). This activation of promoter constructs containing this element by HNF4 was reduced by nearly half by 8-Br-cAMP in H4IIEC3 cells, an effect that was blocked by inhibitors of protein kinase A (PKA). Cotransfection assays showed that COUP-TF I, ARP-1, or PPARδ suppressed the ability of HNF4 to activate the reporter. The repression was potentiated by 8-Br-cAMP. Electrophoretic mobility shift assays revealed that treatment of hepatoma cells or cultured rat hepatocytes with 1 mM 8-Br-cAMP or glucagon reduced binding of FP330-3′ by HNF4 by half. In vitro phosphorylation of HNF4 by PKA decreased binding to FP330-3′. Fasting reduced the ALDH2 protein level in liver and kidney, two tissues expressing HNF4, but not heart. These data suggest that ALDH2 expression can be suppressed by cAMP, most likely through phosphorylation of HNF4 by PKA, and this may account for the reduction in enzyme protein during fasting.

Original languageEnglish (US)
Pages (from-to)79-86
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume398
Issue number1
DOIs
StatePublished - Feb 1 2002

Keywords

  • COUP transcription factors, fasting
  • Cyclic AMP
  • Hepatocyte nuclear factor 4
  • Human aldehyde dehydrogenase 2 promoter

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Fingerprint Dive into the research topics of 'Transcriptional control of the human aldehyde dehydrogenase 2 promoter by hepatocyte nuclear factor 4: Inhibition by cyclic AMP and COUP transcription factors'. Together they form a unique fingerprint.

  • Cite this