Regulation of the murine silver locus product (gp87) by the hypopigmentingcytokines TGF-beta 1 and TNF-alpha

The melanosomal proteins encoded by the silver (si, SILV, or PMEL17) locus play important roles in melanogenesis and are actively investigated as targ ets for melanoma immunotherapy. The human silver locus yields two proteins, gp100 and PMEL17, by alternative splicing of a common mRNA precursor. Mous e melanocytes exclusively express the gp100 orthologue, here termed gp87, t hus providing a simpler model with which to study the silver locus products . We have analyzed the effects of [Nle(4), D-Phe(7)]-alpha melanocyte-stimu lating hormone (alpha MSH) and two hypopigmenting cytokines, tumor necrosis factor (TNF)-alpha. and transforming growth factor (TGF)-beta 1, on the ex pression of gp87 in B16 mouse melanoma cells. TNF-alpha and TGF-beta 1 (at saturating doses for 48 hr) decreased gp87 mRNA by 50%. The gp87 protein wa s almost undetectable by Western immunoblotting after TNF-alpha treatment, but,vas not affected by TGF-beta 1. alpha MSH increased the mRNA and the gp 87 protein similar to 2-fold. Moreover, the amount of gp87,vas not reduced by TNF-cr in the presence of the hormone, in spite of a 50'%, decrease in i ts mRNA. Therefore, the levels of mRNA and gp87 protein did not correlate a fter treatment with the cytokines. Overall, our data suggest that the silve r locus product is not regulated exclusively at the transcriptional level, and highlight the importance of still-uncharacterized regulatory translatio nal and/or post-translational events.