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Okadaic acid-induced transcriptional downregulation of type I collagen gene expression is mediated by protein

Q Wang1, R Raghow

  • 1Department of Pharmacology, College of Medicine, University of Tennessee, Memphis 38104, USA.

Molecular and Cellular Biochemistry
|May 10, 1996
PubMed

Insights

Serine/threonine protein phosphatases (PP) regulate type I collagen gene expression. Protein Phosphatase 2A (PP2A) activation suppresses collagen synthesis, likely via dephosphorylation of key transcription factors.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Type I collagen gene expression is tightly controlled and dysregulated in diseases like fibrosis and cancer.
  • Inflammatory cytokines and signaling pathways involving intracellular phosphorylation significantly impact collagen gene expression.

Purpose of the Study:

  • To investigate the role of serine/threonine protein phosphatases (PP) in regulating type I collagen gene expression.
  • To elucidate the specific involvement of Protein Phosphatase 2A (PP2A) and Protein Phosphatase 1 (PP1) in collagen gene regulation.

Main Methods:

  • Assessed endogenous type I procollagen biosynthesis and Pro alpha 1(I) promoter-luciferase (Luc) construct expression in NIH3T3 fibroblasts.
  • Utilized okadaic acid (OA), a PP2A and PP1 inhibitor, and expressed catalytic subunits of PP2A and PP1.
  • Measured protein synthesis rates, Pro alpha 1(I) collagen mRNA levels, and promoter-driven Luc activity.

Main Results:

  • Okadaic acid (OA) treatment suppressed type I collagen gene expression, indicated by reduced protein synthesis, mRNA levels, and promoter activity.
  • Co-transfection with PP2A expression vectors, but not PP1, stimulated Pro alpha 1(I) collagen promoter activity.
  • These findings suggest OA inhibits collagen gene expression through PP2A-mediated dephosphorylation.

Conclusions:

  • Serine/threonine protein phosphatases, particularly PP2A, play a crucial role in the regulation of type I collagen gene expression.
  • PP2A activation appears to suppress collagen synthesis by dephosphorylating essential transcription factors or cofactors required for Pro alpha 1(I) collagen promoter activation.

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