Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling

Ken ichi Yasumoto, Kazuhisa Takeda, Hideo Saito, Ken ichi Watanabe, Kazuhiro Takahashi, Shigeki Shibahara

Research output: Contribution to journalArticlepeer-review

174 Citations (Scopus)

Abstract

Wnt signals regulate differentiation of neural crest cells through the β-catenin associated with a nuclear mediator of the lymphoid-enhancing factor 1 (LEF-1)/ T-cell factors (TCFs) family. Here we show the interaction between the basic helix-loop-helix and leucine-zipper region of microphthalmia-associated transcription factor (MITF) and LEF-1. MITF is essential for melanocyte differentiation and its heterozygous mutations cause auditory-pigmentary syndromes. Functional cooperation of MITF with LEF-1 results in synergistic transactivation of the dopachrome tautomerase (DCT) gene promoter, an early melanoblast marker. This activation depends on the separate cis-acting elements, which are also responsible for the induction of the DCT promoter by lithium chloride that mimics Wnt signaling. β-catenin is required for efficient transactivation, but dispensable for the interaction between MITF and LEF-1. The interaction with MITF is unique to LEF-1 and not detectable with TCF-1. LEF-1 also cooperates with the MITF-related proteins, such as TFE3, to transactivate the DCT promoter. This study therefore suggests that the MITF/TFE3 family is a new class of nuclear modulators for LEF-1, which may ensure efficient propagation of Wnt signals in many types of cells.

Original languageEnglish
Pages (from-to)2703-2714
Number of pages12
JournalEMBO Journal
Volume21
Issue number11
DOIs
Publication statusPublished - 2002 Jun 3

Keywords

  • Dopachrome tautomerase
  • LEF-1
  • MITF
  • Melanocyte
  • Wnt

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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