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Prenylation differentially inhibits insulin-dependent immediate early gene mRNA expression

J Lee Franklin1, Maggie O Amsler2, Joseph L Messina3

  • 1University of Alabama at Birmingham, Department of Pathology, Division of Molecular and Cellular Pathology, Birmingham, AL 35294, USA.

Biochemical and Biophysical Research Communications
|April 19, 2016
PubMed

Insights

Protein prenylation inhibitors targeting farnesyl transferase (FTase) and geranylgeranyl transferase (GGTase) show potential for treating metabolic diseases. These inhibitors differentially regulate insulin-responsive genes, indicating varied sensitivity in conditions like diabetes and obesity.

Area of Science:

  • Molecular Biology
  • Metabolic Diseases
  • Pharmacology

Background:

  • Elevated prenyl transferase activity is linked to insulin resistance, diabetes, and obesity.
  • Farnesyl transferase (FTase) and geranylgeranyl transferase (GGTase) inhibitors are potential therapeutic agents.

Purpose of the Study:

  • To investigate the effect of acute FTase and GGTase inhibition on insulin-responsive gene expression.
  • To determine if these inhibitors alter gene initiation and/or elongation rates.

Main Methods:

  • Utilized a rat H4IIE hepatoma cell cDNA library to identify insulin-responsive genes (e.g., β-actin, EGR1, Pip92, c-fos, Hsp60).
  • Administered acute treatment with FTase and GGTase inhibitors.
  • Analyzed changes in gene expression, initiation, and elongation rates.

Main Results:

  • Observed differential regulation of insulin-responsive gene expression following inhibitor treatment.
  • Indicated that specific genes exhibit varied sensitivity to FTase and/or GGTase inhibition.

Conclusions:

  • Acute inhibition of protein prenylation pathways differentially affects insulin-responsive gene expression.
  • Suggests distinct molecular mechanisms underlying the regulation of these genes by FTase and GGTase.
Keywords:
Gene expressionImmediate early genesInsulinPrenylationTranscription

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