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.
Yasumoto
Ken-ichi
K
Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
Takeda
Kazuhisa
K
Saito
Hideo
H
Watanabe
Ken-ichi
K
Takahashi
Kazuhiro
K
Shibahara
Shigeki
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D019556:COS Cells; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D051821:Lymphoid Enhancer-Binding Factor 1; D051739:Microphthalmia-Associated Transcription Factor; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051822:T Cell Transcription Factor 1; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D011518:Proto-Oncogene Proteins; D051822:T Cell Transcription Factor 1; C497576:TCF7 protein, human; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase