Alpha-MSH regulates protein ubiquitination in T cells.
The neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) suppresses IFN-gamma + T cells from mice. We discovered, however, that despite this significant production by DTH-mediating effector CD4 supression of IFN-gamma production, alpha-MSH-treated effector T cells had the same level of IFN-gamma mRNA expression and intracellular IFN-gamma protein as untreated activated T cells. In order to explain why IFN-gamma production was suppressed in the face of unchanged mRNA and intracellular IFN-gamma levels, we looked for mechanisms that could increase the degradation of IFN-gamma within the alpha-MSH-treated T cells. Among the known pathways of post-translational intracellular protein modification, the ubiquitin-proteosome system was examined in alpha-MSH-treated T cells to see if a post-translational protein modification occurred to prevent IFN-gamma secretion from the cell. Immunoblots from alpha-MSH-treated T cells showed higher levels of protein ubiquitination when compared to untreated T cells. Resting T cells treated with alpha-MSH also demonstrated enhanced protein ubiquitination. We found that IFN-gamma is one of the ubiquitinated proteins in the alpha-MSH-treated activated T cells. Our results demonstrate that one of the mechanisms by which alpha-MSH regulates T cell activity is through mediating a change in the pattern of protein ubiquitination in T cells.
Biros
D J
DJ
The Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
Namba
K
K
Taylor
A W
AW
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D015151:Immunoblotting; D047468:Immunoprecipitation; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D000521:alpha-MSH / Q000494:pharmacology*
D011506:Proteins; D025801:Ubiquitin; D000521:alpha-MSH; D007371:Interferon-gamma