Regulation of the murine silver locus product (gp87) by the hypopigmenting cytokines TGF-beta1 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 targets for melanoma immunotherapy. The human silver locus yields two proteins, gp100 and PMEL17, by alternative splicing of a common mRNA precursor. Mous...

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Bibliographic Details
Published in:Pigment cell research 2000-04, Vol.13 (2), p.120-126
Main Authors: Martínez-Esparza, M, Jiménez-Cervantes, C, Solano, F, Lozano, J A, García-Borrón, J C
Format: Article
Language:English
Subjects:
alpha-MSH - pharmacology
Animals
Blotting, Northern
Carboxypeptidases - genetics
Carboxypeptidases - metabolism
Gene Expression - drug effects
Gene Expression - physiology
Melanocytes - drug effects
Melanocytes - physiology
Melanoma
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Mice
Pigments, Biological - genetics
Pigments, Biological - metabolism
Protein Biosynthesis - physiology
Proteins
RNA, Messenger - analysis
Transcription, Genetic - physiology
Transforming Growth Factor beta - pharmacology
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha - pharmacology
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Summary: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]-alpha melanocyte-stimulating hormone (alphaMSH) and two hypopigmenting cytokines, tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta1, on the expression of gp87 in B16 mouse melanoma cells. TNF-alpha and TGF-beta1 (at saturating doses for 48 hr) decreased gp87 mRNA by 50%. The gp87 protein was almost undetectable by Western immunoblotting after TNF-alpha treatment, but was not affected by TGF-beta1. alphaMSH increased the mRNA and the gp87 protein approximately 2-fold. Moreover, the amount of gp87 was not reduced by TNF-alpha 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.
ISSN:0893-5785