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)

Among more than 80 different loci related to mouse coat color, microphthalmia-associated transcription factor (Mitf) encoded at the mouse microphthalmia locus is one of the most exciting molecules that regulates the development and survival of many cell types, including melanocyte, retinal pigment epithelium (RPE), and mast cells. Mitf and its human homolog MITF consist of at least three isoforms, referred to as Mitf-A/MITF-A, the heart-type Mitf-H/MITF-H, and the melanocyte lineage-specific Mitf-M/MITF-M, respectively. These isoforms differ in the amino-terminal domains but share a transactivation domain and a basic helix-loop-helix and leucine-zipper structure that is required for DNA binding and dimerization. MITF-M is exclusively expressed in melanocytes and melanoma cells, but not in other cell types, including RPE cells. In contrast, MITF-A mRNA is widely expressed in many cell types. These three isoform mRNAs are possibly generated by differential usage of the gene promoters and by alternative splicing. We predict that the entire MITF gene spans about 200 kb of DNA. Like MITF-M, MITF-A is able to activate the two melanogenesis gene promoters, tyrosinase and tyrosinase-related protein 1. These results suggest that melanogenesis may be regulated by different MITF isoforms in melanocyte and RPE. Possible implications of the multiplicity in Mitf/MITF isoforms are discussed.
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PMID:A big gene linked to small eyes encodes multiple Mitf isoforms: many promoters make light work. 987 May 44

Tyrosinase and a family of tyrosinase-related proteins (TRPs) are melanocyte differentiation gene products involved in melanin pigmentation. Members of the tyrosinase family share upstream transcriptional regulatory elements suggesting that expression of these genes is regulated by shared mechanisms. Microphthalmia transcription factor MITF, a melanocyte-specific basic helix-loop-helix protein, has been shown to transactivate tyrosinase and TRP-1 genes in vitro by binding to a shared regulatory sequence known as M box. The role of MITF in concomitant regulation of these genes in vivo is not clear. We showed earlier that in human melanoma cells TRP-1 can be regulated independently of tyrosinase and pigmentation. To investigate the role of MITF in TRP-1 regulation, we studied the effect of pharmacological agents that modulate transcription of tyrosinase and TRP-1 on MITF. In melanoma cells treated with hexamethylene bisacetamide (HMBA), transcription of TRP-1 gene was selectively and completely inhibited while steady state levels of tyrosinase, TRP-2, MITF mRNA and melanin content showed a modest increase. HMBA caused no detectable change in cellular MITF or its nuclear localization. This MITF-independent regulation of TRP-1 required continued synthesis of RNA and protein. Selective down-regulation of TRP-1 by HMBA occurred even in the presence of cholera toxin which up-regulates TRP-1 by cAMP-mediated pathways. These data show that TRP-1 gene can be down-regulated independently of MITF by de novo activation of negative regulatory factors. Thus, both activation of positive factors such as MITF and inactivation of negative regulatory factors may be required for TRP-1 gene expression during melanocytic differentiation.
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PMID:Role of microphthalmia transcription factor in regulation of melanocyte differentiation marker TRP-1. 1008 Sep 55

Microphthalmia gene encodes a basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor involved in the development of the melanocyte lineage and plays a key role in the transcriptional regulation of the melanogenic enzymes, tyrosinase and TyrpI. Recently, we have shown that Microphthalmia mediates the melanogenic effects elicited by alphaMSH that up-regulates the expression of tyrosinase through the activation of the cAMP pathway. Therefore, Microphthalmia appears as a principal gene in melanocyte development and functioning. Among the transcription factors of the bHLH-Zip family, TFE3 and TFEB show a remarkably elevated homology with Microphthalmia. These observations prompted us to investigate the role of TFE3 and TFEB in the regulation of tyrosinase and TyrpI gene transcription. We show in this report that overexpression of TFE3 stimulates the tyrosinase and TyrpI promoter activities, while TFEB acts only on the TyrpI promoter. TFE3 and TFEB elicit their effects mainly through the binding to Mbox (AGTCATGTGCT) and Ebox motifs (CATGTG) of tyrosinase and TyrpI promoters. In B16 melanoma cells, the high basal expression of TFE3 is down-regulated by forskolin and by alphaMSH. Interestingly, endogenous TFE3 cannot bind as homodimers to the Mbox, and we did not detect TFE3/Mi heterodimers. According to these data, TFE3 is clearly endowed with the capacity to regulate tyrosinase and TyrpI gene expression. However, TFE3 binding to the melanogenic gene promoters is hindered, thereby preventing its potential melanogenic action. In specific physiological or pathological conditions, the recovery of its binding function would make TFE3 an important element in melanogenesis regulation.
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PMID:TFE3, a transcription factor homologous to microphthalmia, is a potential transcriptional activator of tyrosinase and TyrpI genes. 1070 62

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.
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PMID:Involvement of microphthalmia-associated transcription factor (MITF) in expression of human melanocortin-1 receptor (MC1R). 1220 75

The teleost Xiphophorus provides a genetically well-described model system to study the molecular processes underlying melanoma formation. As transcriptional deregulation is a widespread phenomenon in many tumors, we have studied the regulation of melanoma-specific gene expression in this fish. A central regulator of melanocyte specific gene expression, which is also a marker for melanomas, is the transcription factor microphthalmia-associated transcription factor (MITF). One of its targets, the tyrosinase gene, codes for a key enzyme in the melanin synthesis pathway. We could show that the promoter of the medaka tyrosinase gene is highly active in the Xiphophorus melanoma cell line PSM (platyfish-swordtail melanoma) but not in non-melanoma cells. Functional dissection of the promoter revealed that three E-boxes are essential for its pigment cell-specific activity. These binding sites for basic helix-loop-helix transcription factors are recognized by a nuclear protein from the melanoma cell line PSM, most likely MITF, as its exogenous delivery could activate the promoter in non-melanoma cells. The use of specific signalling inhibitors demonstrated that the activity of the tyrosinase promoter is negatively regulated by the melanoma-inducing receptor tyrosine kinase Xmrk in PSM cells. This repression is mediated by MAPkinase and dependent on E-box integrity, again implicating the involvement of MITF. The cumulative evidence indicates that in Xiphophorus, Xmrk suppresses differentiation signals relayed by MITF as part of the transformation process finally resulting in melanoma formation.
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PMID:MITF-M plays an essential role in transcriptional activation and signal transduction in Xiphophorus melanoma. 1459 95

The microphthalmia-associated transcription factor (MITF) gene encodes a basic helix-loop-helix and leucin zipper protein. In this study, we identified a novel MITF isoform, MITF-CM, which possesses a unique amino terminus. Exon 1CM is located 84 kb upstream of the exon encoding the B1b domain. MITF-CM was expressed in the human mast cell line HMC-1, the human basophilic cell line KU812, and CB-derived mast cells cultured for 10 weeks as well as bone marrow mononuclear cells. Transient transfection of MITF-CM cDNA in COS-7 cells resulted in the expression of a 64-kDa protein, detected by Western blotting, and nuclear localization of the protein, detected by immunostaining. The transient cotransfection of a luciferase construct under the control of the tyrosinase promoter and MITF-CM cDNA increased luciferase activity threefold. In contrast, none of the MITF isoforms transactivated both the tryptase and chymase gene promoters, indicating differences in the gene transactivation system between humans and mice.
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PMID:MITF-CM, a newly identified isoform of microphthalmia-associated transcription factor, is expressed in cultured mast cells. 1828 17

Increasing evidence suggests that long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) have roles during biotic and abiotic stress, though their exact contributions remain unclear. To explore their biological functions in response to chilling in bell pepper, we examined their accumulation profiles by deep sequencing and identified 380 lncRNAs, 36 circRNAs, 18 miRNAs, and 4128 differentially expressed mRNAs in the chilled versus the non-chilled fruit. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed differentially expressed genes and putative ncRNA targets, including transcription factors of multiple classes, such as myeloblastosis (MYB), basic helix-loop-helix (bHLH), and ethylene response factor (ERF) transcription factors (TFs), enzymes involved in bio-oxidation and oxidative phosphorylation (serine/threonine-protein kinase, polyphenol oxidase, catalase, peroxidase, lipoxygenase, and ATPase), and cell wall metabolism-related enzymes (beta-galactosidase, pectate lyase, pectinesterase, and polygalacturonase). On the basis of the accumulation profiles, a network of putatively interacting RNAs associated with bell pepper chilling was developed, which pointed to ncRNAs that could provide the foundation for further developing a more refined understanding of the molecular response to chilling injury.
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PMID:Analysis of the Coding and Non-Coding RNA Transcriptomes in Response to Bell Pepper Chilling. 2998 49


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