A ubiquitin-like protein which is synergistically inducible by interferon-gamma and tumor necrosis factor-alpha

A means of regulating the fate of intracellular proteins is their covalent conjugation to ubiquitin-like proteins. A recently discovered ubiquitin-lik e protein is called "diubiquitin" because it consists of two ubiquitin-like domains in head-to-tail arrangement. Human diubiquitin is encoded at the t elomeric end of the MHC class I locus and was previously found to be expres sed in dendritic cells and mature B cells. We have extended the expression analysis of diubiquitin by reverse transcriptase-PCR and Northern blotting in primary endothelial cells and human cancer cell lines derived from nine different tissues. Diubiquitin expression was found to be generally and syn ergistically inducible with the cytokines IFN-gamma and TNF-alpha but not w ith IFN-alpha. Diubiquitin mRNA expression was induced within 2 h after cyt okine stimulation and was independent of protein neosynthesis but dependent on proteasome activity. The mouse homologue of diubiquitin which is also e ncoded in the MHC class I locus was likewise induced with IFN-gamma and TNF -alpha. A general and synergistic induction with IFN-gamma and TNF-alpha su ggests that diubiquitin may exert its functions in antigen presentation or other cellular processes controlled by these two cytokines.