Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tyrosinase promoter has been used to target expression of the mutated human T24 Ha-ras oncogene in pigment-producing cells of transgenic mice. Two independent founder mice carrying the transgene survived and showed the same distinct phenotype of mutated coat color, deeply pigmented skin with multiple nevi, and twirling behavior. The offspring of one of these founders were developed into a line that stably expressed the same phenotype. Histopathological analysis of the tissues revealed hyperpigmentation and/or melanocytic hyperplasia in the skin, eyes, inner ear, and meningeal membranes in the brain. Reverse transcriptase-polymerase chain reaction analysis revealed expression of the transgene in skin, brain, and spleen. We propose that these transgenic mice will be a model for studying the process of multistage melanoma carcinogenesis and a system for evaluating potential chemopreventive agents.
Mol Carcinog 1995 Feb
PMID:Hyperpigmentation and melanocytic hyperplasia in transgenic mice expressing the human T24 Ha-ras gene regulated by a mouse tyrosinase promoter. 766 20

The reaction between mushroom tyrosinase and L-ascorbic acid was studied by oxymetric assays and evidence pointing to ascorbate oxidase activity of this enzyme has been obtained. The activity is clearly linear to enzyme concentration and the Michaelis constant for L-ascorbic acid has a value of 2.69 +/- 0.11 mM. Maximum activity is obtained at pH 7.5. A possible reaction mechanism, which is based on the different enzymatic forms of tyrosinase, is also presented.
Biochem Mol Biol Int 1995 Jun
PMID:Mushroom tyrosinase has an ascorbate oxidase activity. 766 34

Several genes critical to the regulation of melanin production in mammals have recently been cloned and characterized. They map to the albino, brown, and slaty loci in mice, and encode proteins with similar structures and features, but with distinct catalytic capacities. The albino locus encodes tyrosinase, an enzyme with three distinct melanogenic functions, the brown locus encodes TRP1 (tyrosinase-related protein-1), and the slaty locus encodes TRP2, another tyrosinase related-protein. TRP2 functions as DOPAchrome tautomerase, an enzyme that preserves the carboxylic acid content of melanins, which would be spontaneously lost in its absence, while TRP1 is able to oxidize the DHICA produced by TRP2. In this study we have used three different systems (immune-affinity purified melanogenic enzymes, mutant melanocytes, and transfected cells) to examine the enzymatic interactions of these proteins, and their stabilization in a complex which significantly increases their physiological half-life. When extrapolated to the melanocyte, our results demonstrate the catalytic functions of these proteins and suggest how they might stably interact within a melanogenic complex in the melanosome to regulate the quantity and quality of melanin synthesized.
Cell Mol Biol Res 1994
PMID:The tyrosinase gene family--interactions of melanogenic proteins to regulate melanogenesis. 778 79

Tyrosinase (0.2 mg/ml of 0.1 M phosphate buffer solution, pH 6.5) which has cresolase and catecholase activities was irradiated with 60Co gamma-rays. The cresolase activity was measured at varying radiation doses under various atmospheric conditions. D0 was found to be 350 Gy in N2-saturated solution. The OH radical has been shown to be the main species involved in radiation-induced enzyme inactivation. However, in this study, OH radical scavengers, t-BuOH and MeOH, had no effect. O2 which acts generally as an enhancer of OH-induced enzyme inactivation also had little effect, but N20 ae aq scavenger, and Cu++ markedly inhibited the inactivation indicating that e aq is the main species involved in inactivating the cresolase activity, reducing Cu++ as the active center.
Biochem Mol Biol Int 1994 Sep
PMID:Hydrated electron-induced inactivation of tyrosinase in aqueous solution by exposure to cobalt-60 gamma-rays. I. Cresolase activity. 784 40

Tyrosinase (0.2 mg/ml) was irradiated with 60Co gamma-rays. The catecholase activity was measured at varying radiation doses under various atmospheric conditions. D0 was found to be 1.25 kGy and hit number to be 2 in N2-saturated solution. OH radical scavengers, t-BuOH and MeOH, had no effect. O2 which is an enhancer of OH-induced enzyme inactivation had little effect. But N2O as a e aq scavenger and Cu++ markedly protected against the inactivation indicating that e aq was the main species to inactivate the enzymatic activity. By Ultrogel chromatography, it was found that the enzymatic activity was lost when this enzyme dissociated into its subunits. Thus, it was concluded that the radiation-induced inactivation was due to the reduction of Cu++ as the active center and the chelater with e aq followed by the dissociation.
Biochem Mol Biol Int 1994 Sep
PMID:Hydrated electron-induced inactivation of tyrosinase in aqueous solution by exposure to cobalt-60 gamma-rays. II. Catecholase activity. 784 41

Albinism is a group of genetic disorders characterized by deficient synthesis of melanin pigment. In oculocutaneous albinism (OCA) the pigment deficiency involves the skin, hair, and eyes, whereas in ocular albinism (OA) the defect involves principally the visual system. Type I (tyrosinase-deficient) OCA results from deficient catalytic activity of tyrosinase, which catalyzes at least three steps in the melanin biosynthetic pathway. Type II (tyrosinase-positive) OCA results from abnormalities of the 'P' polypeptide, which may be a melanosomal tyrosine transporter. At least some forms of OA appear to represent mild presentations of types I and II OCA. The causes of several other forms of albinism have not yet been identified. Recent application of molecular genetic techniques to the study of these disorders has led to greatly improved knowledge of their molecular pathogenesis and relationships, and paves the way to improved diagnosis, carrier detection and prenatal diagnosis, and even to eventual treatment.
Hum Mol Genet 1994
PMID:Molecular genetics of oculocutaneous albinism. 784 40

Type II (tyrosinase-positive) oculocutaneous albinism (OCA2) is an autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in the skin, hair, and eyes. OCA2, which we have shown results from mutations of the P gene in Caucasians, is the most prevalent type of oculocutaneous albinism in African and African-American patients with OCA. We have identified abnormalities of the P gene in seven unrelated African-American patients with OCA2, including three large deletions, two small in-frame deletions, and six different point mutations. None of these appears to be predominant among African-American patients with OCA2.
Hum Mol Genet 1994 Nov
PMID:Diverse mutations of the P gene among African-Americans with type II (tyrosinase-positive) oculocutaneous albinism (OCA2). 787 25

A full-length cDNA clone encoding apple (Malus domesticus) polyphenol oxidase (PPO) was isolated from a fruit peel cDNA library. Southern analysis indicated that apple PPO is encoded by a divergent multigene family. By northern analysis, PPO mRNA was only detected in a fruit sample taken one week after full bloom. PPO mRNA accumulated in wounded tissues, and also in peel tissue showing the symptoms of superficial scald, a post-harvest disorder. The induction of PPO mRNA provides the first evidence for transcriptional control of PPO expression after wounding or the manifestation of a physiological disorder.
Plant Mol Biol 1995 Jan
PMID:An apple polyphenol oxidase cDNA is up-regulated in wounded tissues. 788 32

The tyrosinase gene is expressed specifically in melanocytes and the cells of the retinal pigment epithelium, which together are responsible for skin, hair, and eye color. By using a combination of DNase I footprinting and band shift assays coupled with mutagenesis of specific DNA elements, we examined the requirements for melanocyte-specific expression of the human tyrosinase promoter. We found that as little as 115 bp of the upstream sequence was sufficient to direct tissue-specific expression. This 115-bp stretch contains three positive elements: the M box, a conserved element found in other melanocyte-specific promoters; an Sp1 site; and a highly evolutionarily conserved element located between -14 and +1 comprising an E-box motif and an overlapping octamer element. In addition, two further elements, one positive and one negative, are located between positions -185 and -150 and positions -150 and -115, respectively. We also found that the basic helix-loop-helix factor encoded by the microphthalmia gene, which is essential for melanocyte differentiation, can transactivate the tyrosinase promoter via the M box and the conserved E box located close to the initiator. Since in vitro assays failed to identify any melanocyte-specific DNA-binding activity, the possibility that the specific arrangement of elements within the basal tyrosinase promoter determines melanocyte-specific expression is discussed.
Mol Cell Biol 1994 Dec
PMID:Melanocyte-specific expression of the human tyrosinase promoter: activation by the microphthalmia gene product and role of the initiator. 796 39

Tyrosinase is a rate-limiting enzyme in melanin biosynthesis and is specifically expressed in differentiated melanocytes. We have identified the enhancer element in the 5'-flanking region of the human tyrosinase gene that is responsible for its pigment cell-specific transcription and have termed it tyrosinase distal element (TDE) (positions -1861 to -1842). Transient expression assays showed that TDE confers efficient expression of a firefly luciferase reporter gene linked to the tyrosinase gene promoter in MeWo pigmented melanoma cells but not in HeLa cells, which do not express tyrosinase. TDE was specifically bound by nuclear proteins of MeWo and HeLa cells, the binding properties of which were indistinguishable in gel mobility shift assays. TDE contains the CATGTG motif in its center, and mutation analysis indicates that the CA dinucleotides of this motif are crucial for protein binding and pigment cell-specific enhancer function. The CATGTG motif is consistent with the consensus sequence recognized by a large family of transcription factors with a basic helix-loop-helix structure, which prompted us to examine the possible involvement of a ubiquitous transcription factor, USF, and a novel factor, microphthalmia-associated transcription factor (MITF), recently cloned as the human homolog of the mouse microphthalmia (mi) gene product. The mi phenotype is associated with a mutant mi locus and characterized by small eyes and loss of melanin pigments. Both USF and MITF are predicted to contain a basic helix-loop-helix structure and a leucine zipper structure. We provide evidence that USF binds to TDE, whereas we were unable to detect the DNA-binding activity of MITF. Transient coexpression assays showed that MITF specifically transactivates the promoter activity of the tyrosinase gene through the CATGTG motif of TDE but not the promoter of the ubiquitously expressed heme oxygenase gene, while USF is able to activate both promoters. These results indicate that MITF is a cell-type-specific factor that is capable of activating transcription of the tyrosinase gene.
Mol Cell Biol 1994 Dec
PMID:Microphthalmia-associated transcription factor as a regulator for melanocyte-specific transcription of the human tyrosinase gene. 786 73


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