Serum concentrations of free ubiquitin and multiubiquitin chains

Ubiquitin, which can conjugate with cellular proteins, is classified into two forms: free ubiquitin and multiubi-quitin chains. The latter is active as a signal for degra-dation of the targeted proteins. We found both forms in human serum and, using two immunoassays, quanti-tated them in sera from healthy subjects and patients with some diseases. Because of putative leakage of erythrocyte ubiquitin, hemolytic serum and serum ob-tained after long incubation (>1–2 h) of blood at room temperature were excluded. Serum concentrations of multiubiquitin chains and free ubiquitin were substan-tially higher in rheumatoid arthritis and hemodialysis patients, respectively, than healthy subjects. Addition-ally, in acute viral hepatitis, serum multiubiquitin chain concentrations were increased in the acute phase, de-creased in the recovery phase, and correlated with ala-nine and aspartate aminotransferase activities (r 5 0.676 and 0.610, P <0.0001 and <0.001, respectively). There-fore, serum ubiquitin may have prognostic value