Proteolysis of NF-kappaB1 p105 is essential for T cell antigen receptor-induced proliferation
To investigate the importance of proteolysis of NF-kappaB1 p105 induced by the kinase IKK in activation of the transcription factor NF-kappaB, we generated 'Nfkb1(SSAA/SSAA)' mice, in which the IKK-target serine residues of p105 were substituted with alanine. Nfkb1(SSAA/SSAA) mice had far...
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| Veröffentlicht in: | Nature immunology 2009-01, Vol.10 (1), p.38-47 |
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| container_title | Nature immunology |
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| creator | Sriskantharajah, Srividya Belich, Monica P Papoutsopoulou, Stamatia Janzen, Julia Tybulewicz, Victor Seddon, Benedict Ley, Steven C |
| description | To investigate the importance of proteolysis of NF-kappaB1 p105 induced by the kinase IKK in activation of the transcription factor NF-kappaB, we generated 'Nfkb1(SSAA/SSAA)' mice, in which the IKK-target serine residues of p105 were substituted with alanine. Nfkb1(SSAA/SSAA) mice had far fewer CD4+ regulatory and memory T cells because of cell-autonomous defects. These T cell subtypes require activation of NF-kappaB by the T cell antigen receptor for their generation, and the Nfkb1(SSAA) mutation resulted in less activation of NF-kappaB in CD4+ T cells and proliferation of CD4+ T cells after stimulation of the T cell antigen receptor. The Nfkb1(SSAA) mutation also blocked the ability of CD4+ T cells to provide help to wild-type B cells during a primary antibody response. IKK-induced p105 proteolysis is therefore essential for optimal T cell antigen receptor-induced activation of NF-kappaB and mature CD4+ T cell function. |
| doi_str_mv | 10.1038/ni.1685 |
| format | Article |
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Nfkb1(SSAA/SSAA) mice had far fewer CD4+ regulatory and memory T cells because of cell-autonomous defects. These T cell subtypes require activation of NF-kappaB by the T cell antigen receptor for their generation, and the Nfkb1(SSAA) mutation resulted in less activation of NF-kappaB in CD4+ T cells and proliferation of CD4+ T cells after stimulation of the T cell antigen receptor. The Nfkb1(SSAA) mutation also blocked the ability of CD4+ T cells to provide help to wild-type B cells during a primary antibody response. 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Nfkb1(SSAA/SSAA) mice had far fewer CD4+ regulatory and memory T cells because of cell-autonomous defects. These T cell subtypes require activation of NF-kappaB by the T cell antigen receptor for their generation, and the Nfkb1(SSAA) mutation resulted in less activation of NF-kappaB in CD4+ T cells and proliferation of CD4+ T cells after stimulation of the T cell antigen receptor. The Nfkb1(SSAA) mutation also blocked the ability of CD4+ T cells to provide help to wild-type B cells during a primary antibody response. 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Nfkb1(SSAA/SSAA) mice had far fewer CD4+ regulatory and memory T cells because of cell-autonomous defects. These T cell subtypes require activation of NF-kappaB by the T cell antigen receptor for their generation, and the Nfkb1(SSAA) mutation resulted in less activation of NF-kappaB in CD4+ T cells and proliferation of CD4+ T cells after stimulation of the T cell antigen receptor. The Nfkb1(SSAA) mutation also blocked the ability of CD4+ T cells to provide help to wild-type B cells during a primary antibody response. IKK-induced p105 proteolysis is therefore essential for optimal T cell antigen receptor-induced activation of NF-kappaB and mature CD4+ T cell function.</abstract><cop>United States</cop><pmid>19060899</pmid><doi>10.1038/ni.1685</doi><tpages>10</tpages></addata></record> |
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| source | MEDLINE; Nature; Alma/SFX Local Collection |
| subjects | Animals CD4-Positive T-Lymphocytes - immunology Cell Differentiation Cell Proliferation I-kappa B Kinase - metabolism Immunologic Memory Lymphocyte Activation - genetics Mice Mice, Knockout Mutation NF-kappa B p50 Subunit - genetics NF-kappa B p50 Subunit - metabolism Receptors, Antigen, T-Cell - agonists Receptors, Antigen, T-Cell - immunology T-Lymphocyte Subsets - immunology T-Lymphocytes, Regulatory - immunology |
| title | Proteolysis of NF-kappaB1 p105 is essential for T cell antigen receptor-induced proliferation |
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