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Microphthalmia‐associated transcription factor interacts with LEF‐1, a mediator of Wnt signaling
Author(s) -
Yasumoto Kenichi,
Takeda Kazuhisa,
Saito Hideo,
Watanabe Kenichi,
Takahashi Kazuhiro,
Shibahara Shigeki
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.11.2703
Subject(s) - microphthalmia associated transcription factor , biology , transactivation , wnt signaling pathway , transcription factor , pax3 , microbiology and biotechnology , leucine zipper , basic helix loop helix , pitx2 , cancer research , genetics , signal transduction , dna binding protein , gene , homeobox
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.