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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2003-5-19
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pubmed:abstractText |
Microphthalmia-associated transcription factor (MITF) contains a basic helix-loop-helix and leucine-zipper (bHLH-LZ) structure and consists of many isoforms with different N-termini. Melanocyte-specific MITF isoform (MITF-M) is of particular interest, because a heterozygous mutation in the MITF gene is associated with Waardenburg syndrome type 2 (WS2) that is characterized by deafness and hypopigmentation because of lack of melanocytes in the inner ear and skin. Expression of MITF-M is under the regulation of the melanocyte-specific promoter (M promoter) of the MITF gene, and transcription from the M promoter is induced by Wnt signals through a nuclear mediator, lymphoid-enhancing factor 1 (LEF-1). In addition, functional cooperation of MITF-M with LEF-1 could lead to transcriptional activation of the M promoter and the dopachrome tautomerase (DCT) gene, an early melanoblast marker. The bHLH-LZ region of MITF-M is responsible for the physical interaction with LEF-1, and beta-catenin is required for the collaboration between LEF-1 and MITF-M. Importantly, MITF-M could function as a non-DNA-binding co-factor for LEF-1. These results suggest that MITF-M may function as a self-regulator of its own expression to maintain a threshold level of MITF-M at a certain sensitive stage of melanocyte development, which could account for the dominant inheritance of WS2. MITF-M therefore plays dual roles in the Wnt signaling pathway; MITF-M represents a downstream target and a nuclear mediator of Wnt signals in melanocytes.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Catnb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intramolecular Oxidoreductases,
http://linkedlifedata.com/resource/pubmed/chemical/LEF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Lef1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphoid Enhancer-Binding Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/MITF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Microphthalmia-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitf protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Zebrafish Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/dopachrome isomerase
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0893-5785
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
261-5
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12753399-Animals,
pubmed-meshheading:12753399-Cell Differentiation,
pubmed-meshheading:12753399-Cytoskeletal Proteins,
pubmed-meshheading:12753399-DNA-Binding Proteins,
pubmed-meshheading:12753399-Exons,
pubmed-meshheading:12753399-Gene Expression Regulation,
pubmed-meshheading:12753399-Heterozygote,
pubmed-meshheading:12753399-Humans,
pubmed-meshheading:12753399-Intramolecular Oxidoreductases,
pubmed-meshheading:12753399-Lymphoid Enhancer-Binding Factor 1,
pubmed-meshheading:12753399-Melanocytes,
pubmed-meshheading:12753399-Mice,
pubmed-meshheading:12753399-Microphthalmia-Associated Transcription Factor,
pubmed-meshheading:12753399-Models, Biological,
pubmed-meshheading:12753399-Models, Genetic,
pubmed-meshheading:12753399-Promoter Regions, Genetic,
pubmed-meshheading:12753399-Protein Binding,
pubmed-meshheading:12753399-Protein Isoforms,
pubmed-meshheading:12753399-Proto-Oncogene Proteins,
pubmed-meshheading:12753399-Signal Transduction,
pubmed-meshheading:12753399-Trans-Activators,
pubmed-meshheading:12753399-Transcription Factors,
pubmed-meshheading:12753399-Transcriptional Activation,
pubmed-meshheading:12753399-Wnt Proteins,
pubmed-meshheading:12753399-Zebrafish Proteins,
pubmed-meshheading:12753399-beta Catenin
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pubmed:year |
2003
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pubmed:articleTitle |
Microphthalmia-associated transcription factor in the Wnt signaling pathway.
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pubmed:affiliation |
Department of Molecular Biology, Tohoku University School of Medicine, Aoba-ku, Sendai, Miyagi, Japan.
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pubmed:publicationType |
Journal Article,
Review,
Research Support, Non-U.S. Gov't
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