• Mouse melanocytes;
  • gp87;
  • Melanogenesis;
  • TGF-β1;
  • TNF-α;
  • Silver locus ;
  • αMSH

The melanosomal proteins encoded by the silver (si, SILV, or PMEL17) locus play important roles in melanogenesis and are actively investigated as targets for melanoma immunotherapy. The human silver locus yields two proteins, gp100 and PMEL17, by alternative splicing of a common mRNA precursor. Mouse melanocytes exclusively express the gp100 orthologue, here termed gp87, thus providing a simpler model with which to study the silver locus products. We have analyzed the effects of [Nle4, d-Phe7]-α melanocyte-stimulating hormone (αMSH) and two hypopigmenting cytokines, tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1, on the expression of gp87 in B16 mouse melanoma cells. TNF-α and TGF-β1 (at saturating doses for 48 hr) decreased gp87 mRNA by 50%. The gp87 protein was almost undetectable by Western immunoblotting after TNF-α treatment, but was not affected by TGF-β1. αMSH increased the mRNA and the gp87 protein ∼2-fold. Moreover, the amount of gp87 was not reduced by TNF-α in the presence of the hormone, in spite of a 50% decrease in its mRNA. Therefore, the levels of mRNA and gp87 protein did not correlate after treatment with the cytokines. Overall, our data suggest that the silver locus product is not regulated exclusively at the transcriptional level, and highlight the importance of still-uncharacterized regulatory translational and/or post-translational events.