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Transcriptional activation of mouse mast cell Protease-7 by activin and transforming growth factor-beta is inhibited

Masayuki Funaba1, Teruo Ikeda, Masaru Murakami

  • 1Laboratory of Nutrition, Azabu University School of Veterinary Medicine, Sagamihara 229-8501, Japan. funaba@azabu-u.ac.jp

The Journal of Biological Chemistry
|October 7, 2003
PubMed

Insights

Activin A and TGF-beta1 up-regulate mouse mast cell protease-7 (mMCP-7) in mast cell progenitors. Microphthalmia-associated transcription factor (MITF) inhibits this process by degrading Smad3, revealing a tissue-specific regulatory mechanism.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Activin A and TGF-beta1 influence mast cell progenitor differentiation.
  • Mouse mast cell protease-7 (mMCP-7) is a marker of differentiated mast cells.

Purpose of the Study:

  • To elucidate the molecular mechanism by which activin A and TGF-beta1 induce mMCP-7 expression.
  • To investigate the role of Smad3 and microphthalmia-associated transcription factor (MITF) in regulating mMCP-7 gene induction.

Main Methods:

  • Utilized bone marrow-derived cultured mast cell progenitors (BMCMCs).
  • Analyzed gene expression of mMCP-7.
  • Investigated protein-protein interactions between Smad3 and MITF.
  • Assessed transcriptional activation and protein degradation pathways.

Main Results:

  • Activin A and TGF-beta1 up-regulated mMCP-7 transcription in BMCMCs via Smad3.
  • MITF inhibited Smad3-mediated mMCP-7 transcription.
  • MITF associated with Smad3, and this interaction led to Smad3 proteasomal degradation.
  • MITF's N-terminal region was crucial for Smad3 interaction and inhibition.

Conclusions:

  • MITF acts as a negative regulator of Smad3-dependent signaling in mast cells.
  • MITF inhibits activin A/TGF-beta1-induced mMCP-7 expression through Smad3 degradation.
  • This study reveals a tissue-specific mechanism controlling mast cell differentiation and function.

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