Abstract
The fine regulation of NF-kappaB activity is crucial for both resting and stimulated cells and relies on complex balance between multiple activators and inhibitors. We report here that c-mip, a recently identified pleckstrin homology (PH) and leucine-rich repeat (LRR)-domain-containing protein, inactivates GSKbeta and interacts with RelA, a key member of the NF-kappaB family. We show that c-mip inhibits the degradation of I-kappaBalpha and impedes the dissociation of the NF-kappaB/I-kappaBalpha complexes. C-mip acts downstream signaling of classical NF-kappaB pathway and may represent one of the missing links in the control of NF-kappaB activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Carrier Proteins / immunology*
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Carrier Proteins / metabolism
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Glycogen Synthase Kinase 3 / immunology*
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Humans
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I-kappa B Proteins / immunology*
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I-kappa B Proteins / metabolism
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Leukocytes, Mononuclear / cytology
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Leukocytes, Mononuclear / immunology*
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Leukocytes, Mononuclear / metabolism
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NF-KappaB Inhibitor alpha
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Protein Structure, Tertiary / physiology
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Signal Transduction / immunology*
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Transcription Factor RelA / immunology*
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Transcription Factor RelA / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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CMIP protein, human
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Carrier Proteins
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I-kappa B Proteins
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NFKBIA protein, human
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RELA protein, human
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Transcription Factor RelA
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NF-KappaB Inhibitor alpha
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Glycogen Synthase Kinase 3 beta
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Glycogen Synthase Kinase 3