Cell-density-dependent regulation of expression and glycosylation of dopachrome tautomerase/tyrosinase-related protein-2.
The expression of the dopachrome tautomerase gene (Dct) and its protein product, tyrosinase-related protein-2, was studied in the cultured, phorbol-ester-dependent murine melanocyte cell line melan-a. Increased cell density was found to stimulate Dct expression both in cells stably transfected with a Dct promoter-lacZ construct and endogenously in nontransfected cells. Increased Dct expression under these conditions corresponds to increased tyrosinase-related protein-2 production. Tyrosinase-related protein-2 was found to exist in two distinct glycoforms with different endoglycosidase sensitivities. Density-dependent expression of tyrosinase-related protein-2 was independent of time of cell growth, cell proliferation, and soluble factors, implying that cell-cell contact is the important determinant governing increased Dct expression under these conditions. Tyrp1 gene expression and tyrosinase-related protein-1 production were also induced under similar conditions. The results show that cell-cell contact between melanocytes induces a coordinated response at both transcriptional and nontranscriptional levels that induces production of the tyrosinase-related proteins that have a significant role in melanization.
Hornyak
T J
TJ
The Ronald O. Perelman Department of Dermatology, New York University Medical Center, New York, USA. thornya1@smtpgw.is.hfh.edu
Hayes
D J
DJ
Ziff
E B
EB
D000818:Animals; D002450:Cell Communication; D002452:Cell Count / Q000187:drug effects*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006031:Glycosylation / Q000187:drug effects; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis / Q000235:genetics*; D010703:Phorbol Esters / Q000494:pharmacology
D010703:Phorbol Esters; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase