In vivo functions of isgylation.

This chapter recapitulates our current knowledge about the functions of the interferon stimulated gene 15 (ISG15) system in vivo with a specific focus on physiological aspects and the biological relevance of ISG15 conjugation and deconjugation. ISG15 contains two domains with structural similarity to ubiquitin and was the first ubiquitin like modifier (UBL) described. It can be conjugated to protein substrates in a process similar to ubiquitin modification termed ISGylation. Of all ubiquitin like modifications ISGylation exhibits the highest degree of interlace with the ubiquitin system and distinct ubiquitin ligases and isopeptidases can also mediate ISG15 linkage and deconjugation, respectively. The system is strongly induced by Type I interferons or microbial infections and studies based on gene targeted mice have shown that it plays an important role in antiviral defence.