Document Detail

Involvement of microphthalmia-associated transcription factor (MITF) in expression of human melanocortin-1 receptor (MC1R).
MedLine Citation:
PMID:  12204775     Owner:  NLM     Status:  MEDLINE    
Analysis of the nucleotide sequence of human melanocortin-1 receptor (MC1R) promoter indicated that an E-box (CANNTG) is present immediately upstream of the transcriptional initiation site. The presence of the CATGTG motif suggests that MC1R gene expression may be regulated by a basic helix-loop-helix-leucine-zipper (bHLH-LZ) type transcription factor. The microphthalmia-associated transcription factor (MITF), which belongs to the family of bHLH-LZ type transcription factors, regulates the transcription of melanogenesis-related enzyme genes such as the tyrosinase and TRP-1 genes. We investigated whether MITF regulates human MC1R gene expression through the same transcriptional mechanism as tyrosinase and TRP-1 genes in melanocytes. For this purpose, the effect of co-expression of cDNA encoding MITF on MC1R promoter activity in NIH/3T3 cells was studied. MC1R promoter activity was induced to the extent of approximately 5-fold in the presence of MITF. In addition, electrophoretic mobility shift assay indicated that nuclear extracts of human SK-Mel-2 cells contain a protein that binds specifically to the MC1R promoter region containing the CATGTG motif. These results suggested that MITF regulates not only the expression of enzymes involved in melanin synthesis, but also the expression of a receptor which plays an essential role in melanocyte functions.
Hirofumi Aoki; Osamu Moro
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Life sciences     Volume:  71     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-09-02     Completed Date:  2002-10-21     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  2171-9     Citation Subset:  IM    
Shiseido Research Center, 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama-shi, Kanagawa 224-8558, Japan.
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MeSH Terms
Base Sequence
Cell Nucleus / genetics
DNA, Complementary / biosynthesis,  genetics
DNA-Binding Proteins / physiology*
Gene Expression Regulation / drug effects
Genes, Reporter / genetics
Luciferases / genetics
Microphthalmia-Associated Transcription Factor
Molecular Sequence Data
Oligonucleotide Probes / diagnostic use
Plasmids / genetics
Receptors, Corticotropin / biosynthesis*,  genetics*
Receptors, Melanocortin
Species Specificity
Transcription Factors / physiology*
Transcriptional Activation / genetics
Tumor Cells, Cultured
beta-Galactosidase / genetics,  metabolism
Reg. No./Substance:
0/DNA, Complementary; 0/DNA-Binding Proteins; 0/MITF protein, human; 0/Microphthalmia-Associated Transcription Factor; 0/Mitf protein, mouse; 0/Oligonucleotide Probes; 0/Receptors, Corticotropin; 0/Receptors, Melanocortin; 0/Transcription Factors; EC 1.13.12.-/Luciferases; EC

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