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Post-transcriptional and post-translational regulation of PTEN by transforming growth factor-beta1

Yong Yang1, Feng Zhou, Zengyu Fang

  • 1Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

Journal of Cellular Biochemistry
|February 12, 2009
PubMed

Insights

Transforming growth factor-beta1 (TGF-β1) reduces tumor suppressor PTEN levels post-transcriptionally and post-translationally. This involves PTEN

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • PTEN is a crucial tumor suppressor gene frequently altered in human cancers.
  • Previous research indicated Transforming growth factor-beta1 (TGF-β1) down-regulates PTEN mRNA in various cell lines.

Purpose of the Study:

  • To investigate the molecular mechanisms by which TGF-β1 affects PTEN expression in hepatocarcinoma cells.
  • To determine if TGF-β1-mediated PTEN down-regulation occurs at the transcriptional, post-transcriptional, or post-translational level.

Main Methods:

  • Dual-luciferase reporter assay to assess PTEN promoter activity.
  • Actinomycin D treatment to analyze PTEN mRNA stability.
  • Transfection studies with PTEN coding sequences.
  • Inhibition of TGF-β receptor (TβRI) and p38 MAPK pathways.
  • Analysis of protein degradation via the ubiquitin-proteasome pathway.

Main Results:

  • TGF-β1 dose- and time-dependently decreased PTEN mRNA and protein levels in SMMC-7721 cells.
  • TGF-β1 did not affect PTEN transcription but accelerated PTEN mRNA degradation post-transcriptionally.
  • The PTEN coding sequence mediated TGF-β1-induced mRNA degradation.
  • Smad and p38 MAPK pathways were involved in TGF-β1-induced PTEN down-regulation.
  • TGF-β1 accelerated PTEN degradation through the ubiquitin-proteasome pathway.

Conclusions:

  • TGF-β1-mediated PTEN down-regulation is a post-transcriptional and post-translational process.
  • The PTEN coding sequence is critical for this regulation.
  • Smad and p38 MAPK signaling pathways play key roles in TGF-β1's effect on PTEN.

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