Ubiquitin-like moiety of the monoclonal nonspecific suppressor factor beta is responsible for its activity.
Monoclonal nonspecific suppressor factor (MNSF), a lymphokine produced by murine T cell hybridoma, possesses pleiotrophic Ag-nonspecific suppressive functions. Most recently, a cDNA clone encoding MNSF beta (a subunit of MNSF) was isolated and characterized. The MNSF beta cDNA encodes a 14.5-kDa fusion protein with MNSF-like activity consisting of an 8-kDa ubiquitin-like segment (ubi-L) and the ribosomal protein S30 (6.5 kDa). To determine whether ubi-L itself has biologic activity, cDNA encoding the ubi-L region was expressed in bacteria and the recombinant product was tested for the activity. Ubi-L showed MNSF-like biologic activity without any cytotoxic action. Interestingly, the addition of ubiquitin to the assay inhibited ubi-L-induced suppression. IFN-gamma, which is known to enhance the expression of MNSF receptor, induced splenocytes to secrete ubi-L by increasing mRNA. Ubi-L has species-specific action and the ability to selectively inhibit the B cell proliferative response stimulated by soluble but not by Sepharose-bound anti-Ig Ab. In addition, okadaic acid, a serine/threonine phosphatase 1 and 2A inhibitor, showed a synergistic inhibitory action with ubi-L, indicative of the possible involvement of phosphatase(s) in the regulation of ubi-L action.
Department of Biochemistry, Shimane Medical University, Izumo, Japan.
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Nakamura
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Xavier
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Tanigawa
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D005260:Female; D006041:Goats; D006801:Humans; D007072:Immunoglobulin D / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019319:Okadaic Acid; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology; D054645:Protein Phosphatase 1; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D012269:Ribosomal Proteins / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013154:Spleen / Q000166:cytology; D013329:Structure-Activity Relationship; D013491:Suppressor Factors, Immunologic / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014452:Ubiquitins / Q000737:chemistry / Q000494:pharmacology
D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D007072:Immunoglobulin D; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D012269:Ribosomal Proteins; D013491:Suppressor Factors, Immunologic; D014452:Ubiquitins; C072169:monoclonal nonspecific suppressor factor; C040469:ribosomal protein S30; D003208:Concanavalin A; D019319:Okadaic Acid; D007371:Interferon-gamma; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1