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

Subjects with elevated serum estrogen concentrations, such as those who are pregnant or ingesting estrogen-containing contraceptive medication, may develop increased skin pigmentation. As little information is available on the mechanism(s) underlying this relationship, the in vitro effects of estrogens on melanocytes cultured from normal human skin were examined. Physiological concentrations of 17 beta-estradiol (10(-11) to 10(-9) M) significantly increased the activity of tyrosinase in melanocytes from 15 of 23 subjects. The observed increases ranged from 1.2- to 2.4-fold. Melanin synthesis, which correlated with tyrosinase activity (r = 0.98, P < 0.001) was increased to a similar extent. Melanin extrusion was also increased by 17 beta-estradiol (10(-9) M). The estrogens, estriol (10(-9) M) and estrone (10(-9) M) stimulated tyrosinase activity and melanin extrusion to a lesser extent than 17 beta-estradiol. The analogue 17 alpha-estradiol (10(-9) M) was shown to have effects on melanocyte tyrosinase activity and melanin extrusion that were equivalent to those of 17 beta-estradiol. The pure estrogen antagonist ICI 164384 (10(-6) M) also stimulated tyrosinase activity. Cycloheximide (50 micrograms/ml) inhibited 17 beta-estradiol-induced tyrosinase stimulation (P < 0.001). These results indicate that several aspects of melanocyte function respond directly to estrogenic stimulation. The equivalent effects of the 17 alpha-analogue and a "pure" anti-estrogen suggest that the 17 beta-estradiol response may be mediated through a non-classical mechanism which is similar to that described in other tissues of neural crest origin.
J Steroid Biochem Mol Biol 1994 May
PMID:Effects of estrogens on human melanocytes in vitro. 800 45

We have previously described tyrosinase-like proteins of rat uterine nuclear extracts with type II estrogen binding characteristics. In this paper we have been able to affinity label these polypeptides with radio-iodinated estradiol. The major label at approximately 33-38 kDa comigrates with a approximately 36 kDa tyrosinase immunoreactive band assessed by autoradiograms and Western blots following electrophoresis. A minor label was also detected at approximately 45 kDa. The label is attenuated by excess quercetin hence these proteins are believed to represent putative type II estrogen binding sites that bind this bioflavonoid. These estrogen binding proteins are distinct from the estrogen receptor as judged by immunoblotting. The affinity crosslinking will be a useful approach in the purification of tyrosinase like proteins.
J Steroid Biochem Mol Biol 1994 Jun
PMID:Estrogen affinity crosslinking to tyrosinase-like immunoreactive proteins of rat uterine nuclear extracts. 803 12

N-Methyl-N-nitrosourea (MNU) is a potent carcinogen that causes the development of murine thymic lymphomas. MNU-induced tumor incidence varies considerably among different inbred mouse strains. In particular, the AKR strain is highly susceptible, whereas the C57L strain is highly resistant to MNU-induced lymphoma formation. Crosses between AKR and C57L mice were established to investigate the genetic basis for the differential susceptibility of these inbred strains. A strong association between MNU-induced lymphoma development and coat color was observed in (AKR x C57)F2 and AKR x (AKR x C57)F1 progeny such that albino mice developed a higher tumor incidence than nonalbino animals. These data suggest that a locus on chromosome 7 influences tumor development. Analysis of four additional polymorphic loci (D7Rp2, Fes, Hbb, and Int-2) on chromosome 7 in AKR x (AKR x C57)F1 backcross mice revealed a significant linkage between high tumor incidence and homozygous inheritance of AKR alleles at the albino (tyrosinase) and Hbb loci. Thus, inheritance of at least one C57L allele at the albino or Hbb loci was associated with protection against MNU-induced lymphoma development. There was no association between tumor incidence and genotype at the D7Rp2, Fes, or Int-2 loci. Taken together, the data suggest that whereas C57L mice contain a dominant tumor suppressor gene on chromosome 7, in the AKR strain both alleles at this locus are defective resulting in enhanced susceptibility to MNU-induced lymphomagenesis.
Mol Carcinog 1993
PMID:Localization of a novel chromosome 7 locus that suppresses development of N-Methyl-N-nitrosourea-induced murine thymic lymphomas. 809 17

We report the isolation and characterization of seven nuclear genes encoding polyphenol oxidase (PPO) in tomato (Lycopersicon esculentum cv. VFNT Cherry). The seven genes (PPOs A, A', B, C, D, E and F) fall into three structural classes (I, II, and III) based on Eco RI and Hind III restriction fragment length polymorphisms (RFLP). RFLP mapping and PFGE analysis demonstrated that the genes reside on chromosome 8, and may be clustered within a 165 kb region. Phage insert mapping demonstrated PPO E and PPO F (both class III), and PPOs B, D and A (classes I, II and I respectively) are grouped within separate 12.4 kb clusters. The complete nucleotide sequence was determined for each gene. Comparison to cDNAs revealed that the PPOs lack introns. A transcript of about 2 kb is expected for each PPO. Each PPO possesses a region encoding a transit peptide characteristic of polypeptides targeted to the thylakoid lumen. Predicted precursor polypeptides range in mass from 66 to 71 kDa and predicted mature polypeptides range from 57 to 62 kDa. All the PPOs encode two putative copper-binding sites characteristic of bacterial, fungal and mammalian tyrosinases. Five of the seven PPOs possess divergent DNA sequences in their 5' promoter regions. These flanking sequence differences may regulate the differential expression of PPO genes.
Plant Mol Biol 1993 Mar
PMID:Organisation of the tomato polyphenol oxidase gene family. 809 28

A catechol oxidase (EC 1.10.3.1) was purified to homogeneity from blood cells of the ascidian Pyura stolonifera using gel filtration on Sephadex G-50 and hydrophobic interaction chromatography on PhenylSuperose. Two peaks of activity were eluted from PhenylSuperose, one with a decreasing salt gradient and the other with nonionic detergent. The latter represents an aggregated form of the enzyme. The enzyme has a molecular weight of 56 kd and shows a preference for catechols with uncharged hydrophobic side chains (e.g., 4-t-butylcatechol) but does not hydroxylate free tyrosine. Inhibition of the enzyme by diethyldithiocarbamic acid and thiol reagents implicate copper at the active site. Sequence analysis of a peptide generated by incubation with Staphylococcus aureus V8 protease demonstrated considerable homology to one of the conserved copper binding regions of tyrosinases. This enzyme is found in the same cells as the dopa-containing protein ferreascidin. When ferreascidin is incubated with the enzyme, its spectrum changes rapidly, indicating that the catechol oxidase uses it as a substrate. The P. stolonifera enzyme differs from an enzyme involved in adhesion, isolated from the mussels, M. edulis and G. demissa: it is isolated as a soluble enzyme that does not appear to exist as a latent precursor.
Mol Mar Biol Biotechnol 1993 Feb
PMID:Purification and properties of a catechol oxidase from blood cells of the ascidian Pyura stolonifera. 810 10

The inhibition by different p-alkoxyphenol derivatives of the growth-regulating enzyme ribonucleotide reductase (RR) in purified Escherichia coli and mouse R2 protein preparations was studied by EPR spectroscopy. The inhibitor-induced inactivation of the catalytic subunit protein R2 was measured at 77 degrees K by observing the decrease of the typical EPR signal from the functionally essential protein-linked tyrosyl free radical. p-Methoxy-, p-ethoxy-, p-propoxy-, and p-allyloxyphenol were about 2 orders of magnitude more effective in inhibiting mouse R2, compared with E. coli R2. Among the p-alkoxyphenols studied, p-propoxyphenol was the most effective inhibitor of mouse R2 (IC50, 0.7 microM) and p-methoxyphenol was the least effective (IC50, 11 microM); p-ethoxy- and p-allyloxyphenol were intermediate. The observed half-maximal inhibition values characterized p-alkoxyphenols as a new class of strong inhibitors of the R2 protein of mammalian RR. p-Propoxy-, p-ethoxy-, and p-allyloxyphenol could be considered as new candidates for anticancer drugs. A special cellular inhibition assay of RR in proliferating tumor cells, in which the tyrosyl radical of R2 at natural concentration was monitored by EPR, showed that the four para-substituted alkoxyphenols also inhibited the enzyme with high efficiency in tumor cells (IC50, between 0.5 microM and 5 microM). Our results with inactivation of protein R2 of RR imply that the cytostatic effect of p-alkoxyphenols on melanoma cells, which has been hitherto explained by inhibition of tyrosinase [Melanoma Res. 2:295-304 (1992)], may be caused at least partly by inhibition of RR. Protein R2 of RR may be considered as an additional target that could be used for future cancer chemotherapy.
Mol Pharmacol 1994 Apr
PMID:p-Alkoxyphenols, a new class of inhibitors of mammalian R2 ribonucleotide reductase: possible candidates for antimelanotic drugs. 818 56

Human and mouse fibroblast chromosomes carrying tyrosinase or b-locus genes were introduced, by microcell hybridization, into pigmented Syrian hamster melanoma cells, and the microcell hybrids were tested for transactivation of the fibroblast tyrosinase and b-locus genes. By using species-specific PCR amplification to distinguish fibroblast and melanoma cDNAs, it was demonstrated that the previously silent fibroblast tyrosinase and b-locus genes were transactivated following chromosomal transfer into pigmented melanoma cells. However, transactivation of the mouse fibroblast tyrosinase gene was unstable in microcell hybrid subclones and possibly dependent on a second fibroblast locus that could have segregated in the subclones. This second locus was not necessary for transactivation of the fibroblast b-locus gene, thus demonstrating noncoordinate transactivation of fibroblast tyrosinase and b-locus genes. Transactivation of the fibroblast tyrosinase gene in microcell hybrids apparently is dependent on the absence of a putative fibroblast extinguisher locus for tyrosinase gene expression, which presumably is responsible for the extinction of pigmentation in hybrids between karyotypically complete fibroblasts and melanoma cells.
Mol Cell Biol 1994 Feb
PMID:Pigment-cell-specific genes from fibroblasts are transactivated after chromosomal transfer into melanoma cells. 828 99

5-Bromodeoxyuridine (BrdU), a thymidine analog, suppresses melanogenesis in Syrian hamster melanoma cells. Tyrosinase, which is the key enzyme for the synthesis of melanin, is suppressed by exposure to BrdU, and the drop in enzyme activity is correlated with a drop in tyrosinase mRNA level. In order to investigate whether suppression of tyrosinase mRNA by BrdU is due to BrdU substitution into coding sequences or upstream sequences of the tyrosinase gene, we carried out stable and transient transfection assays with constructs containing either the human tyrosinase cDNA sequence under the control of a nontyrosinase promoter or a chloramphenicol acetyltransferase (CAT) reporter gene under the control of 5' flanking sequences of the mouse tyrosinase gene. When the plasmid containing the tyrosinase cDNA was stably transfected into mouse fibroblasts, tyrosinase activity in the transfectants was not suppressed by BrdU. Since BrdU would be incorporated into the tyrosinase cDNA integrated in these transfectants, the results suggest that BrdU suppression of tyrosinase gene expression is not due to its incorporation into coding sequences of the tyrosinase gene. When plasmids with tyrosinase regulatory sequences were transfected into melanoma cells for transient expression assays, CAT gene expression was suppressed by BrdU. Because the CAT plasmids do not contain a mammalian origin of replication and should not replicate under the conditions of transient transfection, BrdU would not be incorporated into the DNA of those plasmids. Therefore, these results suggest that the suppression of tyrosinase gene expression by BrdU also is not due to the incorporation of BrdU into upstream sequences of the tyrosinase gene.
Somat Cell Mol Genet 1993 May
PMID:Suppression of tyrosinase gene expression by bromodeoxyuridine in Syrian hamster melanoma cells is not due to its incorporation into upstream or coding sequences of the tyrosinase gene. 833 36

Olfactory marker protein (OMP) shows olfactory neuron-specific expression in rodents. We recently reported tight linkage on mouse chromosome 7 of OMP to the shaker-1 deafness mutant, between the tyrosinase and globin loci. Here we isolate and map the human homologue. Our results show that OMP maps immediately centromeric to tyrosinase on the long arm of human chromosome 11. Genetic linkage to this region has recently been established for Usher Syndrome Type I, an autosomal recessive blindness and deafness disorder and a putative homologue of the shaker-1 mutant. OMP is thus a candidate gene for both congenital deafness defects.
Hum Mol Genet 1993 Feb
PMID:Human olfactory marker protein maps close to tyrosinase and is a candidate gene for Usher syndrome type I. 849 99

Activation with 2-propanol and other organic compounds of prophenoloxidase purified from pupae of Drosophila melanogaster was analyzed. A1, one of the two isozymes of the prophenoloxidase, could be activated with both an endogenous activating system and artificial organic compounds including alcohols. A1 was activated within 2 min after addition of 2-propanol. The phenoloxidase activity of A1, which had been activated with 2-propanol, decreased gradually by lowering the concentration of 2-propanol taking c 60 min to attain a low level, and the activity could be re-elevated at the re-introduction of 2-propanol. Thus the reversibility of the activation of A1 in response to the change of the concentration of 2-propanol in the activating mixture could be observed. Optimum concentration of 2-propanol for the rate of activation was 50%, optimum temperature was 30 degrees C and optimum pH was 7.5. The final level of the phenoloxidase activity, which had been activated with 2-propanol, was higher than that activated with the endogenous activating system. The activated state of A1 showed properties of a tyrosinase-type phenoloxidase. The results suggested that the activation of A1 with 2-propanol is caused by the reversible conformational change of the prophenoloxidase molecule.
Insect Biochem Mol Biol 1993 Jun
PMID:Activation of prophenoloxidase with 2-propanol and other organic compounds in Drosophila melanogaster. 850 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>