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Mol. Cells 2004; 18(2): 200-206

Published online October 31, 2004

© The Korean Society for Molecular and Cellular Biology

IKKγ Inhibits Activation of NF-kB by NIK

Woo Jong Kwon, Sun Hee Kim, Yeo Ok Park, Mong Cho, Chi Dug Kang, Gwang Lee, Woo Gun An, Woo Hong Joo, Dong Wan Kim

Abstract

IKKg is a component of the IKK complex, which regulates NF-kB activity. To investigate the role of IKKg, we expressed wild type IKKg containing 412 amino acids, and deletion mutants containing residues 1-312 and 101-412, using murine IKKg cDNA. In a co-transfection assay with a CAT reporter plasmid, NIK activated NF-kB-dependent gene expression approximately two fold and this expression was inhibited by co-transfection of a wild type IKKg expression plasmid. In binding assays IKKg inhibited the association of IkBa with IKKb and the subsequent phosphorylation of IkBa that is activated by NIK. Inhibition by IKKg also occurred in an assay with a dominant negative mutant of NIK but not with a C-terminal deletion mutant of IKKg, indicating that the C-terminal 100 amino acids of IKKg are important for negative regulation of NF-kB activation. In addition, the interaction of IKKb with IKKg was inhibited by co-transfection with a NIK expression plasmid. Our results suggest that overexpression of IKKg inhibits activation of NF-kB by NIK by competing with NIK for interaction with IKKb.

Keywords IkB Kinases; IKK Complex; IKKg; NF-kB Activation; NIK; Signal Transduction

Article

Research Article

Mol. Cells 2004; 18(2): 200-206

Published online October 31, 2004

Copyright © The Korean Society for Molecular and Cellular Biology.

IKKγ Inhibits Activation of NF-kB by NIK

Woo Jong Kwon, Sun Hee Kim, Yeo Ok Park, Mong Cho, Chi Dug Kang, Gwang Lee, Woo Gun An, Woo Hong Joo, Dong Wan Kim

Abstract

IKKg is a component of the IKK complex, which regulates NF-kB activity. To investigate the role of IKKg, we expressed wild type IKKg containing 412 amino acids, and deletion mutants containing residues 1-312 and 101-412, using murine IKKg cDNA. In a co-transfection assay with a CAT reporter plasmid, NIK activated NF-kB-dependent gene expression approximately two fold and this expression was inhibited by co-transfection of a wild type IKKg expression plasmid. In binding assays IKKg inhibited the association of IkBa with IKKb and the subsequent phosphorylation of IkBa that is activated by NIK. Inhibition by IKKg also occurred in an assay with a dominant negative mutant of NIK but not with a C-terminal deletion mutant of IKKg, indicating that the C-terminal 100 amino acids of IKKg are important for negative regulation of NF-kB activation. In addition, the interaction of IKKb with IKKg was inhibited by co-transfection with a NIK expression plasmid. Our results suggest that overexpression of IKKg inhibits activation of NF-kB by NIK by competing with NIK for interaction with IKKb.

Keywords: IkB Kinases, IKK Complex, IKKg, NF-kB Activation, NIK, Signal Transduction

Mol. Cells
Aug 31, 2022 Vol.45 No.8, pp. 513~602
COVER PICTURE
Cryo-EM structure of human porphyrin transporter ABCB6 (main figure) shows that binding of hemin (inset, magenta) in concert with two glutathione molecules (cyan) primes ABCB6 for high ATP turnover (Kim et al., pp. 575-587).

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