title: Increased level of p27 subunit of proteasomes and its co-localization with tyrosinase in amelanotic melanoma cells indicate its direct role in the regulation of melanin biosynthesis.
abstract: Proteasomes have been shown to be involved in the regulation of melanin biosynthesis in melanoma cells. Here we report on the correlation between proteasome subunits and Tyrosinase (Tyr) activity in different cell phenotypes, and thereby regulation of melanin biosynthesis in B16F10 mouse melanoma cells. Our results indicated that the quantity of proteasome subunit p27 is higher and that of the enzyme Tyr and its activity are lower in amelanotic melanoma cells, while the reverse is true in melanotic melanoma cells. Proteasome subunit p27, compared to another subunit p31, shows increased co-localization with Tyr and Tyrosinase related protein 1 (Trp1) in amelanotic cells to a greater extent than that in melanotic cells. On exposure to cycloheximide, increased Tyr degradation was seen in amelanotic cells, as indicated by increased co-localization of p27 and Tyr. Further, exposure of amelanotic melanoma cells with proteasome-specific inhibitor MG132 resulted in an increased Tyr activity, increased levels of Tyr and Trp1, leading to increased melanin synthesis. These results therefore suggest that proteasomes, particularly p27 subunit, are directly involved in the regulation of melanin biosynthesis in mouse melanoma cells.
authors.affiliation: Cell and Molecular Biology Research Laboratory, Department of Biotechnology, University of Pune, Ganeshkhind, Pune 411 007, Maharastra, India.
authors.forename: Dhanashri
authors.initials: D
authors.lastname: Godbole
authors.forename: Manoj
authors.initials: M
authors.lastname: Mojamdar
authors.forename: Jayanta K
authors.initials: JK
authors.lastname: Pal
mesh_terms: D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D004795:Enzyme Stability / Q000187:drug effects; D007976:Leupeptins / Q000494:pharmacology; D008543:Melanins / Q000096:biosynthesis*; D018328:Melanoma, Amelanotic / Q000201:enzymology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D014176:Protein Biosynthesis / Q000187:drug effects; D021122:Protein Subunits / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects
chemical_list: D007976:Leupeptins; D008543:Melanins; D061988:Proteasome Inhibitors; D021122:Protein Subunits; D003513:Cycloheximide; D010088:Oxidoreductases; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde