Abstract
NF-kappa B is usually activated by signal-induced, ubiquitin-mediated degradation of its inhibitor, I kappa B. This process is initiated by phosphorylation of I kappa B by the I kappa B kinase (IKK) complex, predominantly by the IKK beta catalytic subunit, and requires the regulatory subunit IKK gamma (NEMO). Another activation pathway, with no known physiological inducers, involves ubiquitin-mediated processing of the NF-kappa B2 inhibitory protein p100 and is dependent on phosphorylation of p100 by IKK alpha. We show here that B cell-activating factor (BAFF) activates this second pathway and that this requires the BAFF receptor (BAFF-R), the NF-kappa B-inducing kinase (NIK) and protein synthesis, but not NEMO. This NEMO-independent cascade is physiologically relevant for the survival and, hence, progression of maturing splenic B cells.
MeSH terms
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Animals
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B-Cell Activating Factor
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B-Cell Activation Factor Receptor
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B-Lymphocytes / cytology
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B-Lymphocytes / metabolism*
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Cell Differentiation
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Cell Survival
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I-kappa B Kinase
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Membrane Proteins / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Mice, Knockout
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NF-kappa B / metabolism*
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NF-kappa B p50 Subunit
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NF-kappa B p52 Subunit
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NF-kappaB-Inducing Kinase
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Protein Processing, Post-Translational*
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Protein Serine-Threonine Kinases / metabolism*
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Receptors, Tumor Necrosis Factor / metabolism
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Time Factors
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Tumor Necrosis Factor-alpha / metabolism*
Substances
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B-Cell Activating Factor
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B-Cell Activation Factor Receptor
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Membrane Proteins
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NF-kappa B
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NF-kappa B p50 Subunit
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NF-kappa B p52 Subunit
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Tumor Necrosis Factor
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Tnfrsf13c protein, mouse
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Tnfsf13b protein, mouse
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Tumor Necrosis Factor-alpha
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Protein Serine-Threonine Kinases
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Chuk protein, mouse
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I-kappa B Kinase
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Ikbkb protein, mouse
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Ikbke protein, mouse