Proteome analysis reveals ubiquitinâconjugating enzymes to be a new family of interferonâαâregulated genes
2000
Nyman, Tuula A. | Matikainen, Sampsa | Sareneva, Timo | Julkunen, Ilkka | Kalkkinen, Nisse
Interferon (IFN)âα is a cytokine with antiviral, antiproliferative, and immunomodulatory properties, the functions of which are mediated via IFNâinduced protein products. We used metabolic labeling and twoâdimensional gel electrophoresis followed by MS and database searches to identify potentially new IFNâαâinduced proteins in human Tâcells. By this analysis, we showed that IFNâα induces the expression of ubiquitin crossâreactive protein (ISG15) and two ubiquitinâconjugating enzymes, UbcH5 and UbcH8. Northernâblot analysis showed that IFNâα rapidly enhances mRNA expression of UbcH5, UbcH6 and UbcH8 in Tâcells. In addition, these genes were induced in macrophages in response to IFNâα or IFNâγ stimulation or influenzaâA or Sendai virus infections. Similarly, IFNs enhanced UbcH8 mRNA expression in A549 lung epithelial cells, HepG2 hepatoma cells, and NKâ92 cells. Cycloheximide, a protein synthesis inhibitor, did not block IFNâinduced upregulation of UbcH8 mRNA expression, suggesting that UbcH8 is the primary target gene for IFNâα and IFNâγ. Ubiquitin conjugation is a rateâlimiting step in antigen presentation and therefore the upregulation of UbcHs by IFNs may contribute to the enhanced antigen presentation by macrophages. Our results show that proteome analysis of cells is a suitable method for identifying previously unrecognized cytokineâinducible genes.
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