Transcriptional Activation of Mouse Mast Cell Protease-7 by Activin and Transforming Growth Factor-β Is Inhibited by Microphthalmia-associated Transcription Factor

Masayuki Funaba, Teruo Ikeda, Masaru Murakami, Kenji Ogawa, Kunihiro Tsuchida, Hiromu Sugino, Matanobu Abe

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Previous studies have revealed that activin A and transforming growth factor-β1 (TGF-β1) induced migration and morphological changes toward differentiation in bone marrow-derived cultured mast cell progenitors (BMC-MCs). Here we show up-regulation of mouse mast cell protease-7 (mMCP-7), which is expressed in differentiated mast cells, by activin A and TGF-β1 in BMCMCs, and the molecular mechanism of the gene induction of mmcp-7. Smad3, a signal mediator of the activin/ TGF-β pathway, transcriptionally activated mmcp-7. Microphthalmia-associated transcription factor (MITF), a tissue-specific transcription factor predominantly expressed in mast cells, melanocytes, and heart and skeletal muscle, inhibited Smad3-mediated mmcp-7 transcription. MITF associated with Smad3, and the C terminus of MITF and the MH1 and linker region of Smad3 were required for this association. Complex formation between Smad3 and MITF was neither necessary nor sufficient for the inhibition of Smad3 signaling by MITF. MITF inhibited the transcriptional activation induced by the MH2 domain of Smad3. In addition, MITF-truncated N-terminal amino acids could associate with Smad3 but did not inhibit Smad3-mediated transcription. The level of Smad3 was decreased by co-expression of MITF but not of dominant-negative MITF, which resulted from proteasomal protein degradation. The changes in the level of Smad3 protein were paralleled by those in Smad3-mediated signaling activity. These findings suggest that MITF negatively regulates Smad-dependent activin/TGF-β signaling in a tissue-specific manner.

Original languageEnglish
Pages (from-to)52032-52041
Number of pages10
JournalJournal of Biological Chemistry
Volume278
Issue number52
DOIs
Publication statusPublished - 26-12-2003

Fingerprint

Microphthalmia-Associated Transcription Factor
Activins
Transforming Growth Factors
Transcriptional Activation
Chemical activation
Mast Cells
Transcription
Smad3 Protein
Mouse Tpsab1 protein
Tissue
Melanocytes
Proteolysis
Muscle
Cultured Cells
Myocardium
Bone
Skeletal Muscle
Transcription Factors
Up-Regulation
Genes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Funaba, Masayuki ; Ikeda, Teruo ; Murakami, Masaru ; Ogawa, Kenji ; Tsuchida, Kunihiro ; Sugino, Hiromu ; Abe, Matanobu. / Transcriptional Activation of Mouse Mast Cell Protease-7 by Activin and Transforming Growth Factor-β Is Inhibited by Microphthalmia-associated Transcription Factor. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 52. pp. 52032-52041.
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abstract = "Previous studies have revealed that activin A and transforming growth factor-β1 (TGF-β1) induced migration and morphological changes toward differentiation in bone marrow-derived cultured mast cell progenitors (BMC-MCs). Here we show up-regulation of mouse mast cell protease-7 (mMCP-7), which is expressed in differentiated mast cells, by activin A and TGF-β1 in BMCMCs, and the molecular mechanism of the gene induction of mmcp-7. Smad3, a signal mediator of the activin/ TGF-β pathway, transcriptionally activated mmcp-7. Microphthalmia-associated transcription factor (MITF), a tissue-specific transcription factor predominantly expressed in mast cells, melanocytes, and heart and skeletal muscle, inhibited Smad3-mediated mmcp-7 transcription. MITF associated with Smad3, and the C terminus of MITF and the MH1 and linker region of Smad3 were required for this association. Complex formation between Smad3 and MITF was neither necessary nor sufficient for the inhibition of Smad3 signaling by MITF. MITF inhibited the transcriptional activation induced by the MH2 domain of Smad3. In addition, MITF-truncated N-terminal amino acids could associate with Smad3 but did not inhibit Smad3-mediated transcription. The level of Smad3 was decreased by co-expression of MITF but not of dominant-negative MITF, which resulted from proteasomal protein degradation. The changes in the level of Smad3 protein were paralleled by those in Smad3-mediated signaling activity. These findings suggest that MITF negatively regulates Smad-dependent activin/TGF-β signaling in a tissue-specific manner.",
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Transcriptional Activation of Mouse Mast Cell Protease-7 by Activin and Transforming Growth Factor-β Is Inhibited by Microphthalmia-associated Transcription Factor. / Funaba, Masayuki; Ikeda, Teruo; Murakami, Masaru; Ogawa, Kenji; Tsuchida, Kunihiro; Sugino, Hiromu; Abe, Matanobu.

In: Journal of Biological Chemistry, Vol. 278, No. 52, 26.12.2003, p. 52032-52041.

Research output: Contribution to journalArticle

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AU - Funaba, Masayuki

AU - Ikeda, Teruo

AU - Murakami, Masaru

AU - Ogawa, Kenji

AU - Tsuchida, Kunihiro

AU - Sugino, Hiromu

AU - Abe, Matanobu

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