Activation of the tyrosinase gene promoter by neurofibromin.
Neurofibromatosis type 1 (NF1) is a hereditary cancer syndrome, characterized by café-au-lait skin spots and multiple neurofibromas. A gene linked to NF1 encodes neurofibromin, an established function of which is to stimulate intrinsic GTPase activity of ras protein. By transiently coexpressing a neurofibromin cDNA in a melanoma cell line, we show that neurofibromin increases the expression of a reporter gene under the control of the tyrosinase gene promoter. Tyrosinase is a rate-limiting enzyme in melanin biosynthesis and is expressed only in melanin-producing cells. Functional analysis of neurofibromin cDNAs suggests that the domain related to a GTPase-activating protein is mainly responsible for this induction. These results suggest that neurofibromin functions as a regulator of melanogenesis, a process specific to the melanocytes derived from the neural crest.
Suzuki
H
H
Department of Applied Physiology and Molecular Biology, Tohoku University School of Medicine, Miyagi, Japan.
Takahashi
K
K
Yasumoto
K
K
Shibahara
S
S
D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D016514:Genes, Neurofibromatosis 1; D006367:HeLa Cells; D006801:Humans; D014442:Monophenol Monooxygenase / Q000235:genetics*; D009456:Neurofibromatosis 1 / Q000201:enzymology / Q000235:genetics; D025542:Neurofibromin 1; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D011506:Proteins / Q000235:genetics / Q000494:pharmacology*; D051381:Rats
D018076:DNA, Complementary; D025542:Neurofibromin 1; D011506:Proteins; D014442:Monophenol Monooxygenase