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A PPAR response element regulates transcription of the gene for human adipose differentiation-related protein

Author

  • Paul Targett-Adams
  • Marion J McElwee
  • Ewa Ehrenborg
  • Mattias Gustafsson
  • Colin N Palmer
  • John McLauchlan

Summary, in English

Lipid droplets are cytoplasmic organelles which serve as storage sites for neutral lipids. Adipose differentiation-related protein (ADRP) is intrinsically associated with the surface of lipid droplets and is believed to play a major role in the maintenance of lipid stores in non-adipocytes. ADRP abundance is intimately linked to the amount of lipid found within cells and agents which increase the levels of intracellular lipid, such as certain agonists of the peroxisome proliferator-activated receptors (PPARs), also are capable of modulating ADRP gene transcription. However, little is known about the molecular mechanisms and promoter control elements, which regulate the transcription of the human gene. Using a reporter system to investigate ADRP transcription, we have identified a PPAR response element (PPRE) with the sequence 5'-AGGTGA A AGGGCG-3' within its promoter region. Mutational analysis revealed that the ADRP PPRE specifically mediated the upregulation of transcription in response to activation by agonists of PPAR subtypes alpha and delta in both rat and human hepatocyte-derived cell lines. These findings offer insight into the mechanisms which serve to regulate ADRP transcription and intracellular lipid storage.

Publishing year

2005

Language

English

Pages

95-104

Publication/Series

Biochimica et Biophysica Acta, Gene Structure and Expression

Volume

1728

Issue

1-2

Document type

Journal article

Publisher

Elsevier

Topic

  • Immunology in the medical area
  • Microbiology in the medical area

Keywords

  • PPRE
  • Promoter
  • ADRP
  • Regulation
  • PPAR

Status

Published

ISBN/ISSN/Other

  • ISSN: 0167-4781