Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regulation of the mouse tyrosinase gene expression is controlled by a highly conserved element at -100 bp, the M-box, and an enhancer at -12 kb. In most vertebrates, the length of intergenic sequences makes it difficult to analyze the whole gene and the complete regulatory region. We took advantage of the compact Fugu genome to identify regulatory regions involved in pigment cell-specific expression. We isolated the Fugu tyrosinase gene, and identified putative cis-acting regulatory elements within the promoter. We then asked whether the Fugu promoter sequence functions in mouse pigment cells. We showed that E11.5 transgenic embryos bearing 6 kb or 3 kb of Fugu tyrosinase 5' sequence fused to the reporter gene lacZ revealed melanoblast and RPE-specific expression. This is the first evidence that the tyrosinase promoter is active at midgestation in melanoblasts, long before the onset of pigmentation.
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PMID:The Fugu rubripes tyrosinase gene promoter targets transgene expression to pigment cells in the mouse. 1110 50

In this study, we have addressed the impact of the mouse tyrosinase enhancer on regulated expression from the mouse tyrosinase promoter during embryonic development. Stable and transient transgenic experiments using the reporter gene lacZ reveal that (1) expression is detected in neural crest-derived melanoblasts from E11.5 onward, (2) the enhancer does not increase transgenic expression in optic cup-derived pigment cells of the retinal pigment epithelium (RPE), and (3) expression in the telencephalon is not any longer detected. The importance of the enhancer for expression in pigment cells of the eye was further investigated in adult mice using an attenuated diphtheria toxin A gene. This demonstrated that in presence of the enhancer the transgene expression is specifically targeted to neural crest-derived melanocytes of the choroid and not, or slightly, to the RPE. This suggests that tyrosinase is differentially regulated in the two pigment cell lineages, and that this promoter can be used to target expression preferentially to the neural crest-derived melanocyte lineage.
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PMID:Increased transgene expression by the mouse tyrosinase enhancer is restricted to neural crest-derived pigment cells. 1130 51

The Odd Sex mouse mutation arose in a transgenic line of mice carrying a tyrosinase minigene driven by the dopachrome tautomerase (Dct) promoter region. The minigene integrated 0.98 Mb upstream of Sox9 and was accompanied by a deletion of 134 kb. This mutation causes female to male sex reversal in XX Ods/+ mice, and a characteristic eye phenotype of microphthalmia with cataracts in all mice carrying the transgene. Ods causes sex reversal in the absence of Sry by upregulating Sox9 expression and maintaining a male pattern of Sox9 expression in XX Ods/+ embryonic gonads. This expression, which begins at E11.5, triggers downstream events leading to the formation of a testis. We report here that the 134 kb deletion, in itself, is insufficient to cause sex reversal. We demonstrate that in Ods, the Dct promoter is capable of acting over a distance of 1 Mb to induce inappropriate expression of Sox9 in the retinal pigmented epithelium of the eye, causing the observed microphthalmia. In addition, it induces Sox9 expression in the melanocytes where it causes pigmentation defects. We propose that Ods sex reversal is due to the Dct promoter element interacting with gonad-specific enhancer elements to produce the observed male pattern expression of Sox9 in the embryonic gonads.
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PMID:Long-range activation of Sox9 in Odd Sex (Ods) mice. 1511 64

Melanin is a major factor that darkens skin color as one of the defense systems to prevent the harmful effects of UV light. However, darkened skin from the localized or systemic accumulation of melanin is viewed in many cultures as an esthetic problem. Consequentially, searching for antimelanogenic agents from natural sources is very popular worldwide. Previous screening of fermented rice products, obtained from various rice cultivars fermented with different sources of loog-pang (Thai traditional fermentation starter), revealed that the highest ability to reduce the melanin content in B16F10 melanoma cells was from unpolished black rice fermented with a defined starter mixture of microbes isolated from loog-pang E11. The aim of this study was to investigate the mechanism of the fermented unpolished black rice (FUBR) on the inhibition of melanogenesis in B16F10 melanoma cells. The strongest reduction of cellular melanin content was found in the FUBR sap (FUBRS). The melanin reduction activity was consistent with the significant decrease in the intracellular tyrosinase activity. The FUBRS showed no cytotoxic effect to B16F10 melanoma or Hs68 human fibroblast cell lines. It also significantly reduced the transcript and protein expression levels of tyrosinase, tyrosinase-related protein 1 (TYRP-1), TYRP-2, and microphthalmia-associated transcription factor. Furthermore, it induced a significantly increased level of phosphorylated ERK, p38 and Akt signaling pathways, which likely contributed to the negative regulation of melanogenesis. From these results, a model for the mechanism of FUBRS on melanogenesis inhibition was proposed. Moreover, these results strongly suggested that FUBRS possesses antimelanogenesis activity with high potential for cosmeceutical application as a skin depigmenting agent.
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PMID:Fermented Unpolished Black Rice (Oryza sativa L.) Inhibits Melanogenesis via ERK, p38, and AKT Phosphorylation in B16F10 Melanoma Cells. 3242 83