Selective down‐regulation of tyrosinase family gene TYRP1 by inhibition of the activity of melanocyte transcription factor, MITF

摘要: Tyrosinase (TYR), tyrosinase-related protein-1 (TYRP1/gp75) and dopachrome tautomerase (DCT/ TYRP2) belong to a family of melanocyte-specific gene products involved in melanin pigmentation. During melanocyte development expression tyrosinase genes is thought be orchestrated part by the binding shared basic helix‐loop‐helix transcription factor MITF M box, regulatory element conserved among these genes. In transformed melanocytes, TYRPs highly variable. Whereas TYR melanoma cells regulated both transcriptional post-translational mechanisms, TYRP1/gp75 often completely extinguished during tumor progression. this study, we investigated mechanisms selective repression TYRP1 transcription. Interestingly, early stage mRNA could induced inhibition protein synthesis. Transient transfection experiments with minimal promoter showed that activity correlates endogenous gene. Nucleotide deletion analysis revealed novel sequences attenuate box-dependent activity, but which are not TYRP1. Gel mobility shift box selectively inhibited ‐ cells. These data suggest factors modulate repress presumably other target