FIGURE 5.

A model of the relationship between ISGylation and nitrosylation. Immune response induces the expression of ISG15 and iNOS. Induced ISG15 is used for ISG15 modification (ISGylation) of many substrates and contributes to protein translation regulation and anti-virus effect. ISG15 itself can prevent the replication of human immunodeficiency virus. ISG15 also induces interferon-γ production and has chemotactic activity. Some of the induced ISG15 forms homodimer, which is an inactive form and cannot be used for ISGylation. The nitric oxide produced mainly by iNOS contributes to the nitrosylation of ISG15 and prevents the dimerization of ISG15, which means more free monomer ISG15 is available for ISGylation.