Abstract
Schnurri (Shn)-2 is a large zinc finger-containing protein implicated in cell growth, signal transduction and lymphocyte development. Here, we report that Shn-2-deficient (Shn-2(-/-)) mice develop CD3-positive lymphoma spontaneously. In Shn-2(-/-) mice, we observed decreased cytotoxicity of natural killer (NK) cells accompanied by decreased expression of perforin and granzyme-B. In addition, phosphorylation of signal transducer and activator of transcription (STAT) 5 was reduced in Shn-2(-/-) NK cells, while phosphorylation of STAT3 and protein expression of nuclear factor-κB p65 subunit were enhanced in Shn-2(-/-) NK cells. Moreover, cell-surface expression of activation molecules such as CD27, CD69 and CD122 were decreased on Shn-2(-/-) NK cells. Thus, Shn-2 is considered to play an important role in the activation and function of NK cells and the development of T cell lymphoma in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD3 Complex / analysis
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Cytotoxicity, Immunologic
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Granzymes / analysis
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Immunity, Innate
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Immunologic Surveillance
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Interleukin-2 / pharmacology
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Longevity / genetics
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Lung / pathology
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Lymphocyte Activation
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Lymphoma, T-Cell / genetics*
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Lymphoma, T-Cell / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / deficiency
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology*
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Perforin / analysis
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Specific Pathogen-Free Organisms
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Spleen / pathology
Substances
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CD3 Complex
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DNA-Binding Proteins
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Hivep2 protein, mouse
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Interleukin-2
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Neoplasm Proteins
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Perforin
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Granzymes
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Gzmb protein, mouse