Effects of interferon gamma and major histocompatibility complex-encoded subunits on peptidase activities of human multicatalytic proteases.
We have examined several peptidase activities of human multicatalytic protease (MCP) purified from the lymphoblastoid cell line 721.45 and a deletion mutant derivative, 721.174, lacking MCP subunits encoded in the major histocompatibility complex (MHC) class II region. Wild-type lymphoblast MCP hydrolyzed a specific peptide, glutaryl-Gly-Gly-Phe-4-methylcoumaryl-7-amide (-MCA), several times faster than the mutant enzyme did, suggesting that MHC-encoded subunits may provide this activity. Contrary to a recent report [Driscoll, J., Brown, M. G., Finley, D. & Monaco, J J. (1993) Nature (London) 365, 262-264], we did not detect significant aminopeptidase associated with lymphoblast MCPs. Our results also differ markedly from those of Gaczynska et al. [Gaczynska, M., Rock, K. L. & Goldberg, A L. (1993) Nature (London) 365, 264-267], who reported that gamma interferon (IFN-gamma) alters the peptidase activities of lymphoblast MCPs. We found that IFN-gamma did not produce significant differences in the peptidase activities of purified MCPs. Moreover, our measurements of Vmax and Km for succinyl-Leu-Leu-Val-Tyr-MCA hydrolysis differ 600-fold and 15-fold, respectively, from those reported by Gaczynska et al. On balance, the findings presented here do not support the idea that IFN-gamma induces major changes in the peptidase activity of purified MCPs.
Ustrell
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V
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City 84132.
Pratt
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Rechsteiner
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M
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000302:isolation & purification; D017951:Antigen Presentation; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000187:drug effects / Q000378:metabolism*; D004912:Erythrocytes / Q000201:enzymology; D006412:Hematopoietic Stem Cells / Q000201:enzymology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008214:Lymphocytes / Q000201:enzymology; D008285:Major Histocompatibility Complex / Q000235:genetics; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D013379:Substrate Specificity
D000949:Histocompatibility Antigens Class II; D009097:Multienzyme Complexes; D010455:Peptides; D007371:Interferon-gamma; D000626:Aminopeptidases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex