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.
Keywords:
Bcl-G; ERK; T cell; ubiquitin-like protein.
MeSH terms
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Animals
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Antibodies, Monoclonal / pharmacology
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Apoptosis
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B-Lymphocytes / cytology
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B-Lymphocytes / drug effects
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B-Lymphocytes / metabolism
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CD28 Antigens / genetics*
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CD28 Antigens / metabolism
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CD3 Complex / genetics*
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CD3 Complex / metabolism
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Cell Line
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Cell Proliferation
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Cell Survival
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Gene Expression Regulation*
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Interleukin-4 / biosynthesis
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Interleukin-4 / metabolism
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Mice
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Mice, Inbred BALB C
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / genetics
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Mitogen-Activated Protein Kinase 3 / metabolism
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Primary Cell Culture
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Protein Binding
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Proto-Oncogene Proteins c-bcl-2 / genetics*
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Signal Transduction
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Spleen / cytology
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Spleen / drug effects
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Spleen / metabolism
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Suppressor Factors, Immunologic / genetics*
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Suppressor Factors, Immunologic / metabolism
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / drug effects
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T-Lymphocytes, Helper-Inducer / metabolism*
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Transfection
Substances
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Antibodies, Monoclonal
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BCL2L14 protein, mouse
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CD28 Antigens
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CD3 Complex
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Proto-Oncogene Proteins c-bcl-2
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Suppressor Factors, Immunologic
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monoclonal nonspecific suppressor factor
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Interleukin-4
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3