The present invention relates to regulation of inflammation. More particularly, the present invention is directed to nucleic acids encoding components of the ubiquitin ligation pathway, e.g., ubiquitin and ubiquitin-like molecules, E1, E2, and E3 proteins and their substrates, which are involved in modulation of the inflammatory process. The invention further relates to methods for identifying and using agents, including small molecule chemical compositions, antibodies, peptides, cyclic peptides, nucleic acids, RNAi, antisense nucleic acids, and ribozymes, that modulate the inflammatory process via modulation of the ubiquitin ligation pathway; as well as to the use of expression profiles and compositions in diagnosis and therapy related to regulation of inflammation and modulation of cytokine signaling involved in inflammation, e.g., for treatment of infection, autoimmune disease and other diseases related to the inflammatory process.