Eumelanin biosynthesis is regulated by coordinate expression of tyrosinase and tyrosinase-related protein-1 genes.
Melanin is specifically produced in melanocytes. The pathway for melanin biosynthesis is regulated by a number of melanocyte-specific proteins, including tyrosinase and tyrosinase-related protein-1 (TRP-1, b locus protein). To understand the regulation of melanogenesis, we examined tyrosinase activities, mRNA levels of tyrosinase and TRP-1, and eumelanin and pheomelanin contents in mouse B16-F1 melanoma cells after they had been treated with some melanotropic reagents. Cholera toxin, alpha-melanocyte-stimulating hormone, and dibutyryl cyclic AMP increased tyrosinase activity and stimulated eumelanin biosynthesis. These reagents elevated intracellular cAMP levels. In contrast, 12-O-tetradecanoylphorbol 13-acetate reduced tyrosinase activity and eumelanin synthesis. In all cases, the mRNA levels of tyrosinase and TRP-1 changed in parallel with tyrosinase activity and eumelanin content. TRP-1 was induced simultaneously with tyrosinase, although its inducibility was lower than that of tyrosinase. These results suggest that the expressions of tyrosinase and TRP-1 genes are coordinately regulated by melanotropic reagents through cAMP-dependent protein kinase and protein kinase C in mouse B16-F1 cells, and that their coordinate expression causes eumelanin biosynthesis.
Kuzumaki
T
T
Department of Biochemistry, Yamagata University School of Medicine, Japan.
Matsuda
A
A
Wakamatsu
K
K
Ito
S
S
Ishikawa
K
K
D000818:Animals; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic; D005809:Genes, Regulator; D008543:Melanins / Q000096:biosynthesis*; D008562:Membrane Glycoproteins; D051379:Mice; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000235:genetics* / Q000378:metabolism; D010088:Oxidoreductases; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D012313:RNA / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects; D000521:alpha-MSH / Q000494:pharmacology
D008543:Melanins; D008562:Membrane Glycoproteins; D010703:Phorbol Esters; D011506:Proteins; C041877:eumelanin; D000521:alpha-MSH; D012313:RNA; D003994:Bucladesine; D002772:Cholera Toxin; D000242:Cyclic AMP; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D011494:Protein Kinases; D011493:Protein Kinase C