Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling.
Wnt signals regulate differentiation of neural crest cells through the beta-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. beta-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.
Mesh Terms:
Amino Acid Sequence, Animals, Base Sequence, Blotting, Western, COS Cells, DNA, Complementary, DNA-Binding Proteins, Genes, Reporter, Hela Cells, Humans, Intramolecular Oxidoreductases, Lymphoid Enhancer-Binding Factor 1, Microphthalmia-Associated Transcription Factor, Models, Biological, Molecular Sequence Data, Mutation, Plasmids, Promoter Regions, Genetic, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, T Cell Transcription Factor 1, Transcription Factors, Transcriptional Activation, Transfection, Two-Hybrid System Techniques, Wnt Proteins, Zebrafish Proteins
Amino Acid Sequence, Animals, Base Sequence, Blotting, Western, COS Cells, DNA, Complementary, DNA-Binding Proteins, Genes, Reporter, Hela Cells, Humans, Intramolecular Oxidoreductases, Lymphoid Enhancer-Binding Factor 1, Microphthalmia-Associated Transcription Factor, Models, Biological, Molecular Sequence Data, Mutation, Plasmids, Promoter Regions, Genetic, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, T Cell Transcription Factor 1, Transcription Factors, Transcriptional Activation, Transfection, Two-Hybrid System Techniques, Wnt Proteins, Zebrafish Proteins
EMBO J.
Date: Jun. 03, 2002
PubMed ID: 12032083
View in: Pubmed Google Scholar
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