Nuclear role of I kappa B Kinase-gamma/NF-kappa B essential modulator (IKK gamma/NEMO) in NF-kappa B-dependent gene expression.
The I kappa B kinase (IKK) complex, which is composed of the two kinases IKK alpha and IKK beta and the regulatory subunit IKK gamma/nuclear factor-kappa B (NF-kappa B) essential modulator (NEMO), is important in the cytokine-induced activation of the NF-kappa B pathway. In addition to modulation of IKK activity, ... the NF-kappa B pathway is also regulated by other processes, including the nucleocytoplasmic shuttling of various components of this pathway and the post-translational modification of factors bound to NF-kappa B-dependent promoters. In this study, we explored the role of the nucleocytoplasmic shuttling of components of the IKK complex in the regulation of the NF-kappa B pathway. IKK gamma/NEMO was demonstrated to shuttle between the cytoplasm and the nucleus and to interact with the nuclear coactivator cAMP-responsive element-binding protein-binding protein (CBP). Using both in vitro and in vivo analysis, we demonstrated that IKK gamma/NEMO competed with p65 and IKK alpha for binding to the N terminus of CBP, inhibiting CBP-dependent transcriptional activation. These results indicate that, in addition to the key role of IKK gamma/NEMO in regulating cytokine-induced IKK activity, its ability to shuttle between the cytoplasm and the nucleus and to bind to CBP can lead to transcriptional repression of the NF-kappa B pathway.
Mesh Terms:
Blotting, Western, Cell Line, Cell Nucleus, Cyclic AMP Response Element-Binding Protein, Cytoplasm, Fatty Acids, Unsaturated, Glutathione Transferase, HeLa Cells, Humans, I-kappa B Kinase, Luciferases, Microscopy, Confocal, Microscopy, Fluorescence, NF-kappa B, Plasmids, Precipitin Tests, Promoter Regions, Genetic, Protein Binding, Protein Processing, Post-Translational, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Recombinant Fusion Proteins, Transcription, Genetic, Transcriptional Activation, Transfection
Blotting, Western, Cell Line, Cell Nucleus, Cyclic AMP Response Element-Binding Protein, Cytoplasm, Fatty Acids, Unsaturated, Glutathione Transferase, HeLa Cells, Humans, I-kappa B Kinase, Luciferases, Microscopy, Confocal, Microscopy, Fluorescence, NF-kappa B, Plasmids, Precipitin Tests, Promoter Regions, Genetic, Protein Binding, Protein Processing, Post-Translational, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Recombinant Fusion Proteins, Transcription, Genetic, Transcriptional Activation, Transfection
J. Biol. Chem.
Date: Jan. 30, 2004
PubMed ID: 14597638
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