title: Ubiquitin-like protein MNSFβ negatively regulates T cell function and survival.
abstract: Monoclonal non-specific suppressor factor β (MNSFβ) is a ubiquitously expressed member of the ubiquitin-like family that is involved in various biological functions. Previous studies have demonstrated that MNSFβ covalently binds to intracellular pro-apoptotic protein Bcl-G and regulates apoptosis in macrophages. In this study, we demonstrate that MNSFβ negatively regulates T cell function. In murine T-helper type 2 clone, D10.G4.1 (D10) cells transfected with MNSFβ cDNA, CD3/CD28-induced ERK1/2 phosphorylation leading to IL-4 production was significantly inhibited. The formation of MNSFβ-Bcl-G complex was induced by the CD3/CD28 stimulation. Co-transfection with MNSFβ and Bcl-G greatly enhanced CD3/CD28-induced apoptosis in D10 cells. Similarly, co-over-expression of MNSFβ and Bcl-G caused a marked enhancement of apoptosis in purified splenic T cells. Interestingly, this MNSFβ adduct was also induced in T cells derived from DO11.10 mice stimulated with antigen. Collectively, CD3/CD28-inducible MNSFβ-Bcl-G complex may be involved in the regulation of T cell function and survival.
authors.affiliation: Department of Cooperative Medical Research, Collaboration Center, Shimane University , Izumo , Japan.
authors.forename: Morihiko
authors.initials: M
authors.lastname: Nakamura
authors.forename: Mai
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Jun
authors.initials: J
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018106:CD28 Antigens / Q000235:genetics* / Q000378:metabolism; D017252:CD3 Complex / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D005786:Gene Expression Regulation; D015847:Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013491:Suppressor Factors, Immunologic / Q000235:genetics* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; C576156:BCL2L14 protein, mouse; D018106:CD28 Antigens; D017252:CD3 Complex; D019253:Proto-Oncogene Proteins c-bcl-2; D013491:Suppressor Factors, Immunologic; C072169:monoclonal nonspecific suppressor factor; D015847:Interleukin-4; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Bcl-G; ERK; T cell; ubiquitin-like protein