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TRAIL inhibited the cyclic AMP responsible element mediated gene expression

Yasuhito Tokumoto1, Katsuhisa Horimoto, Jun Miyake

  • 1Department of Bioengineering, The University of Tokyo, Bunkyo-ku, Japan. y.tokumoto@will.dpc.u-tokyo.ac.jp

Biochemical and Biophysical Research Communications
|February 24, 2009
PubMed

Insights

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) down-regulates gene expression controlled by the cyclic AMP responsive element (CRE) enhancer. This finding was observed in NIH3T3 cells using reporter assays and gene expression analysis.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Biochemistry

Background:

  • Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis in tumor cells.
  • TRAIL also influences other cellular functions, including transcription factor activation.
  • The precise impact of TRAIL on specific gene regulatory pathways remains an area of investigation.

Purpose of the Study:

  • To investigate the effect of TRAIL administration on gene expression regulated by the cyclic AMP responsive element (CRE) enhancer.
  • To determine if TRAIL influences the activity of signaling pathways involving CRE.

Main Methods:

  • Utilized the signal transduction reporter cis-element plasmid pCRE-d2EGFP to monitor CRE-driven gene expression.
  • Employed Western blotting to quantify the expression levels of the reporter protein d2EGFP.
  • Performed DNA Chip (gene expression) time series analysis to assess changes in endogenous gene expression.

Main Results:

  • Administration of TRAIL led to down-regulation of the d2EGFP reporter protein in NIH3T3 cells.
  • DNA Chip analysis confirmed TRAIL-induced down-regulation of gene expression controlled by the CRE enhancer.
  • Expression levels of six genes containing a CRE sequence in their promoter region were slightly decreased within three hours of TRAIL administration.

Conclusions:

  • TRAIL negatively regulates gene expression downstream of the CRE enhancer.
  • TRAIL affects cellular functions through modulation of CRE-mediated transcription.
  • These findings reveal a novel mechanism of TRAIL action on gene expression regulation.

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