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

We have identified a Tsp509I polymorphism in the 3' UTR of the human tyrosinase related protein-1 gene (TYRP). TYRP is one of several genes involved in melanin pigment production.
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PMID:Detection of a Tsp509I polymorphism in the 3' UTR of the human tyrosinase related protein-1 (TYRP) gene. 786 80

The use of lentiviral vectors for basic research and potential future clinical applications requires methodologies that can accurately determine lentiviral titers and monitor viral transgene expression within target cells, beyond the context of reporter genes typically used for this purpose. Here we describe a quantitative RT-PCR (qRT-PCR) method that achieves both goals using primer sequences that are specific for the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE), an enhancer contained in many retroviral vectors and that is incorporated in the 3' UTR of nascent transgene transcripts. Quantitation of titers of three recombinant lentiviruses, genetically identical except for the transgene, demonstrated consistent differences in titer that were likely due to transgene-associated toxicity in producer cells and target cells. Viruses encoding the tumor-associated antigens tyrosinase and neo-poly(A) polymerase yielded reproducibly lower titers than a virus encoding enhanced green fluorescent protein (GFP) at the viral RNA, integrated DNA, and transgene mRNA levels, as measured by WPRE qPCR. Furthermore, the magnitude of differences in expression of the three transgenes in transduced target cells could not have been predicted by measuring vector DNA integration events. Since transgene expression in target cells is the most common goal of lentiviral transduction, and since methods to quantify transgene expression on the protein level are not always readily available, qRT-PCR based on a nucleotide sequence included in the transcript provides a useful tool for titering novel recombinant lentiviruses.
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PMID:Real-time quantitative reverse transcriptase-polymerase chain reaction as a method for determining lentiviral vector titers and measuring transgene expression. 1271 61

The microphthalmia-associated transcription factor (MITF) is a pivotal regulator of melanogenic enzymes for melanogenesis, and its expression is modulated by many transcriptional factors at the transcriptional level or post-transcriptional level through microRNAs (miRNAs). Although several miRNAs modulate melanogenic activities, there is no evidence of their direct action on MITF expression. Out of eight miRNAs targeting the 3'-UTR of Mitf predicted by bioinformatic programs, our results show miR-218 to be a novel candidate for direct action on MITF expression. Ectopic miR-218 dramatically reduced MITF expression, suppressed tyrosinase activity, and induced depigmentation in murine immortalized melan-a melanocytes. MiR-218 also suppressed melanogenesis in human pigmented skin organotypic culture (OTC) through the repression of MITF. An inverse correlation between MITF and miR-218 expression was found in human primary skin melanocytes and melanoma cell lines. Taken together, our findings demonstrate a novel mechanism involving miR-218 in the regulation of the MITF pigmentary process and its potential application for skin whitening therapy.
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PMID:MicroRNA-218 inhibits melanogenesis by directly suppressing microphthalmia-associated transcription factor expression. 2482 43

It has been demonstrated that microRNAs (miRNAs) play important roles in the control of melanogenesis and hair color in mammals. By comparing miRNA expression profiles between brown and white alpaca skin, we previously identified miR508-3p as a differentially expressed miRNA suggesting its potential role in melanogenesis and hair color formation. The present study was conducted to determine the role of miR508-3p in melanogenesis in alpaca melanocytes. In situ hybridization showed that miR508-3p is abundantly present in the cytoplasma of alpaca melanocytes. miR508-3p was predicted to target the gene encoding microphthalmia transcription factor (MITF) and a luciferase reporter assay indicated that miR508-3p regulates MITF expression by directly targeting its 3'UTR. Overexpression of miR508-3p in alpaca melanocytes down-regulated MITF expression both at the messenger RNA and protein level and resulted in decreased expression of key melanogenic genes including tyrosinase and tyrosinase-related protein 2. Overexpression of miR508-3p in melanocytes also resulted in decreased melanin production including total alkali-soluble melanogenesis, eumelanogenesis and pheomelanogenesis. Results support a functional role of miR508-3p in regulating melanogenesis in alpaca melanocytes by directly targeting MITF.
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PMID:Role of microRNA508-3p in melanogenesis by targeting microphthalmia transcription factor in melanocytes of alpaca. 2740 15

It has been demonstrated that microRNAs (miRNAs) play important roles in the regulation of melanogenesis and hair color in mammals. Short tandem target mimic (STTM) has been used to effectively block small RNA functions in plants and animals. We previously showed that miR508-3p plays a functional role in regulating melanogenesis in alpaca melanocytes by directly targeting microphthalmia (MITF). To verify the effect of miR-508-3p function on melanogenesis in alpaca melanocytes, miR-508-3p was blocked using STTM technology in the present research. miR508-3p was predicted to target the gene encoding SRY-box6 (SOX6) by bioinformatics. The luciferase reporter assay indicated that miR508-3p regulates SRY-box6 (SOX6) expression by targeting its 3'UTR. Here, STTM-miR508-3p overexpression in alpaca melanocytes blocked the expression of miR-508-3p and up-regulated SOX6 expression at both the mRNA and protein levels, resulting in increasing the expression of key melanogenic genes, including cAMP responsive element (CRE) binding protein (CREB), MITF, tyrosinase (TYR) and tyrosinase-related protein 1 and 2 (TYRP1 and TYRP2). STTM-miR508-3p overexpression in melanocytes also resulted in increased melanin production, including total alkali soluble melanogenesis (ASM), eumelanogenesis (EM) and pheomelanogenesis (PM). Additionally, we identified melanin granules in alpaca melanocytes transfected with STTM-miR508-3p under Fontana-Masson staining. These results suggest that STTM-miR508-3p could up-regulate melanogenesis by effectively blocking miR508-3p.
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PMID:Effect of silencing microRNA-508 by STTM on melanogenesis in alpaca (Vicugna pacos). 3009 30