- melanin and skin pigmentation
- Biochemical Analysis and Sensing Techniques
- RNA regulation and disease
- Cancer, Hypoxia, and Metabolism
- Cell death mechanisms and regulation
- Mitochondrial Function and Pathology
- Endoplasmic Reticulum Stress and Disease
- RNA Interference and Gene Delivery
- Wnt/β-catenin signaling in development and cancer
- Ubiquitin and proteasome pathways
- Advanced biosensing and bioanalysis techniques
- Toxic Organic Pollutants Impact
- Mast cells and histamine
- Retinoids in leukemia and cellular processes
- DNA and Nucleic Acid Chemistry
- RNA Research and Splicing
- High Altitude and Hypoxia
- Advanced Fluorescence Microscopy Techniques
- Adipose Tissue and Metabolism
- Autophagy in Disease and Therapy
- Invertebrate Immune Response Mechanisms
- Epigenetics and DNA Methylation
- Hair Growth and Disorders
- Click Chemistry and Applications
- Photochromic and Fluorescence Chemistry
Tohoku University
2010-2023
Ibaraki University
2008
Hitachi (Japan)
2008
National Institutes of Health
2002-2007
Cancer Institute (WIA)
2007
National Cancer Institute
2002-2006
Center for Biologics Evaluation and Research
2002
National Heart Lung and Blood Institute
2002
Institute for Rheumatic Diseases (Japan)
1994
Tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2 are the enzymes involved in melanin biosynthesis preferentially expressed pigment cells. Their human gene promoters share 11-base pair M box containing a CATGTG motif, which was shown here to be bound vitro by microphthalmia-associated transcription factor (MITF). Transient cotransfection analysis showed that MITF overexpression increased expression of reporter under control tyrosinase or TRP-1 promoter but not promoter. The...
Microphthalmia-associated transcription factor (Mitf) plays a critical role in the development of neural crest-derived melanocytes. Here, we show that exogenously added Wnt-3a protein, an intercellular signaling molecule, up-regulates expression endogenous melanocyte-specific Mitf (Mitf-M) mRNA cultured The promoter humanMITF gene (MITF-M promoter) contains functional LEF-1-binding site, which is bound vitro by LEF-1 and confers preferential on reporter melanocytes melanoma cells, as judged...
We investigated whether or not the topographic regulation of melanocyte differentiation is determined by mesenchymal-epithelial interactions via fibroblast-derived factors. The density in palmoplantar human skin (i.e., on palms and soles) five times lower than that found nonpalmoplantar sites. Palmoplantar fibroblasts significantly suppressed growth pigmentation melanocytes compared with fibroblasts. Using cDNA microarray analysis, derived from expressed high levels dickkopf 1 (DKK1; an...
The epidermis (containing primarily keratinocytes and melanocytes) overlies the dermis fibroblasts) of human skin. We previously reported that dickkopf 1 (DKK1) secreted by fibroblasts in elicits hypopigmented phenotype palmoplantar skin due to suppression melanocyte function growth via regulation two important signaling factors, microphthalmia-associated transcription factor (MITF) beta-catenin. now report treatment with DKK1 increases their proliferation decreases uptake melanin...
Melanin is a heterogeneous biopolymer produced only by specific cells termed melanocytes, which synthesize and deposit the pigment in specialized membrane-bound organelles known as melanosomes. Although melanosomes have been suspected of being closely related to lysosomes platelets, total number melanosomal proteins still unknown. Thus far, six melanosome-specific identified, challenge characterize complete proteome melanosome further understand its mechanism biogenesis. In this report, we...
Pigmentation of the hair, skin, and eyes mammals results from a number melanocyte-specific proteins that are required for biosynthesis melanin. Those comprise structural enzymatic components melanosomes, membrane-bound organelles in which melanin is synthesized deposited. Tyrosinase (TYR) absolutely melanogenesis, but other melanosomal proteins, such as TYRP1, DCT, gp100, also play important roles regulating mammalian pigmentation. However, pigmentation does not always correlate with...
Waardenburg syndrome type 2 (WS2) is an autosomal dominant disorder characterized by a combination of pigmentary and auditory abnormalities. Approximately 20% WS2 cases are associated with mutations in the gene encoding microphthalmia-associated transcription factor (MITF). MITF plays critical role development both neural-crest-derived melanocytes optic cup-derived retinal pigmented epithelium (RPE); loss functional Mitf mice results complete absence all pigment cells, which turn induces...
Tyrosinase is a rate-limiting enzyme in melanin biosynthesis and specifically expressed differentiated melanocytes. We have identified the enhancer element 5'-flanking region of human tyrosinase gene that responsible for its pigment cell-specific transcription termed it distal (TDE) (positions -1861 to -1842). Transient expression assays showed TDE confers efficient firefly luciferase reporter linked promoter MeWo pigmented melanoma cells but not HeLa cells, which do express tyrosinase. was...
Waardenburg syndrome type 2 (WS2) is associated with heterozygous mutations in the gene encoding microphthalmia-associated transcription factor (MITF) and characterized by deafness hypopigmentation due to lack of melanocytes inner ear skin. Melanocyte-specific MITF isoform (MITF-M) essential for melanocyte differentiation transcriptionally induced Wnt signaling that mediated β-catenin LEF-1. Here we show MITF-M transactivates its own promoter (Mpromoter) interacting LEF-1, as judged...
We have cloned and sequenced the human genomic DNA segments encoding 5'-flanking region first two exons of DOPAchrome tautomerase (DT)/tyrosinase-related protein 2 (TRP-2) gene. The DT gene is a member tyrosinase family specifically expressed in melanin-producing cells. A transcriptional initiation site was identified by S1 nuclease-mapping primer-extension analyses using RNA prepared from pigmented melanoma To study mechanism for pigment cell-specific expression gene, we analyzed promoter...
A novel cis-acting regulatory element (designated BTE for basic transcription element) was found in the region proximal to TATA sequence of P-450c gene by use deletion mutations. This DNA is considered be involved and does not show distinct enhancer activity itself. Together with XRE (A. Fujisawa-Sehara, K. Sogawa, M. Yamane, Y. Fujii-Kuriyama, Nucleic Acids Res. 15:4179-4191, 1987), however, this required a high inducible expression response xenobiotic inducers. The contained GC box...
Microphthalmia-associated transcription factor (MITF) is a basic helix-loop-helix-leucine zipper protein, and plays an important role in the development of various cell types, such as neural-crest-derived melanocytes optic-cup-derived retinal pigment epithelium. Three isoforms MITF with distinct amino-termini have been described. These include melanocyte lineage-specific MITF-M, heart-type MITF-H, recently identified MITF-A. Here we identify fourth isoform, MITF-C, unique amino-terminus 34...