Induction of melanocyte-specific microphthalmia-associated transcription factor by Wnt-3a

Kazuhisa Takeda, Ken Ichi Yasumoto, Ritsuko Takada, Shinji Takada, Ken Ichi Watanabe, Tetsuo Udono, Hideo Saito, Kazuhiro Takahashi, Shigeki Shibahara

Research output: Contribution to journalArticlepeer-review

257 Citations (Scopus)


Microphthalmia-associated transcription factor (Mitf) plays a critical role in the development of neural crest-derived melanocytes. Here, we show that exogenously added Wnt-3a protein, an intercellular signaling molecule, up-regulates the expression of endogenous melanocyte-specific Mitf (Mitf-M) mRNA in cultured melanocytes. The melanocyte-specific promoter of the human MITF gene (MITF-M promoter) contains a functional LEF-1-binding site, which is bound in vitro by LEF-1 and confers the preferential expression on a reporter gene in melanocytes and melanoma cells, as judged by the transient transfection assays. Moreover, the LEF-1-binding site is required for the transactivation of a reporter gene by LEF-1, β-catenin, or their combination. Exogenously added Wnt-3a protein also transactivates the MITF-M promoter via the LEF-1-binding site; this activation was abolished when a dominant-negative form of LEF-1 was coexpressed. These results suggest that Wnt-3a signaling recruits β-catenin and LEF-1 to the LEF-1-binding site of the MITF-M promoter. Therefore, the present study identifies Mitf-M/MITF-M as a direct target of Wnt signaling.

Original languageEnglish
Pages (from-to)14013-14016
Number of pages4
JournalJournal of Biological Chemistry
Issue number19
Publication statusPublished - 2000 May 12

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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