Nuclear role of I kappa B Kinase-gamma/NF-kappa B essential modulator (IKK gamma/NEMO) in NF-kappa B-dependent gene expression

• Published in: The Journal of biological chemistry Vol. 279; no. 5; pp. 3509 - 3515
• Main Authors: Verma, Udit N, Yamamoto, Yumi, Prajapati, Shashi, Gaynor, Richard B
• Format: Journal Article
• Language: English
• Published: United States 30-01-2004
• Subjects: Blotting, Western; Cell Line; Cell Nucleus - metabolism; Cyclic AMP Response Element-Binding Protein - metabolism; Cytoplasm - metabolism; Fatty Acids, Unsaturated - pharmacology; Glutathione Transferase - metabolism; HeLa Cells; Humans; I-kappa B Kinase; Luciferases - metabolism; Microscopy, Confocal; Microscopy, Fluorescence; NF-kappa B - metabolism; Plasmids - metabolism; Precipitin Tests; Promoter Regions, Genetic; Protein Binding; Protein Processing, Post-Translational; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases - metabolism; Protein-Serine-Threonine Kinases - physiology; Recombinant Fusion Proteins - metabolism; Transcription, Genetic; Transcriptional Activation; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M309300200

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.