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)

Tyrosinase-related protein (TRP)-1 is one of the most abundant melanosomal glycoproteins involved in melanogenesis. This report summarizes our recent research efforts related to the biological role and biosynthesis of TRP-1 and its transport from TGN (trans-Golgi network) to the stage I melanosome. Our UV irradiation and tyrosinase and TRP-1 cDNA co-transfection studies indicated that human TRP-1 is involved in not only melanogenesis but also prevention of melanocyte death, which may occur during biosynthesis of melanin pigment in the presence of tyrosinase. Furthermore, a coordinated gene interaction was indicated between tyrosinase and TRP-1, resulting in upregulation of mRNA and protein expression of LAMP (lysosome-associated membrane protein)-1 that would directly prevent the tyrosinase-mediated programmed cell death of melanocytes. Similar to tyrosinase, however, TRP-1 appears to require a molecular chaperone, calnexin, which we have cloned recently. Our cDNA transfection study of tyrosinase with calnexin showed clearly the necessity of calnexin in order to have efficient, functional activity of melanosomal glycoprotein, especially tyrosinase. Once glycosylation is completed, TRP-1 will be transported from TGN to the stage I melanosome. At this stage, TRP-1 will have its own target signal, in particular, tyrosine-rich leucine residues in cytoplasmic tail. Our TRP-1 cDNA transfection and immunoelectron microscopy study shows that TRP-1 will be transported through small vesicles, probably non-clathrin-coated type, to large vacuoles, identical to the MPR (mannose-6-phosphate receptor)-positive, late endosomes. In this transport process a low molecular weight G-protein, rab-7, was isolated from the purified melanosomal protein on 2D-PAGE and identified by subsequent sequencing and PCR amplification. Confocal microscopy with double immunostaining and immunoelectron microscopy confirmed the co-localization of rab-7 and TRP-1 in the melanosomes with early stages of maturation (I-HI). Furthermore, this process will also be regulated by phosphatidylinositol 3-kinase (PI-3 kinase).
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PMID:Biological role of tyrosinase related protein and its biosynthesis and transport from TGN to stage I melanosome, late endosome, through gene transfection study. 926 27

The 3beta-(2-diethylaminoethoxy)-androstenone HCl (U18666A), progesterone and several cationic amphiphilic drugs have been shown to alter the trafficking of a number of intracellular membrane proteins including CD63/Lamp-3, insulin growth factor 2/mannose 6-phosphate receptor (IGF2/MPR), and the Niemann-Pick C1 gene product (NPC1) as well as ganglioside GM1. We have examined the effects of these compounds on cultured melanocytes at concentrations that have been shown to effectively alter intracellular trafficking. Treatment of melanocytes with U18666A (2.5 micro M) or progesterone (15 micro M) for 96 h decreased melanin content an average of 67% as compared with control without lowering the total cellular tyrosinase activity. Steroidal alkaloids that preferentially act on the Sonic Hedgehog signaling pathway showed no related specificity in their ability to decrease pigmentation. In melanocytes treated with U18666A, tyrosinase accumulates in a compartment that contains both lysosome-associated membrane protein-1 (Lamp 1) and MPR, and stains with filipin, consistent with cholesterol-laden late endosomes/lysosomes. Our results suggest that tyrosinase, like the NPC1 gene product, traverses a U18666A-sensitive trafficking pathway.
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PMID:Accumulation of tyrosinase in the endolysosomal compartment is induced by U18666A. 1262 92