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KMID : 0613820160260090991
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Journal of Life Science
2016 Volume.26 No. 9 p.991 ~ p.998
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Hsp70 and IKKγ Synergistically Suppress the Activation of NF-κB
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Kim Mi-Jeong
Kim Ka-Hye
Kim Moon-Jeong
Kim Jin-Ik
Choi Hye-Jung
Moon Ja-Young
Joo Woo-Hong
Kim Dong-Wan
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Abstract
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NF-κB acts as a critical transcription factor for the survival of cells via the induction of antiapoptotic genes. Constitutive activation of NF-κB in many types of solid tumors suggests that the inhibition of NF-κB might prevent or inhibit tumorigenesis. Although a number of studies demonstrated that Hsp70 regulated NF-κB activity, the exact mechanism is not clear. This study investigated the functional relationship of Hsp70 and IKKγ in the regulation of NF-κB activation using expression plasmids of components of the IKK complex. Wild-type and deletion mutants of IKKγ were expressed together with Hsp70, and the combined regulatory effect of Hsp70 and IKKγ on NF-κB activation was assayed. Hsp70 suppressed the activation of NF-κB in a reporter plasmid assay. Hsp70 also suppressed the phosphorylation and degradation of IκBα. The suppressive effect of Hsp70 on NF-κB activation was synergistically elevated by IKKγ. The N-terminal IKKβ binding site, C-terminal leucine zipper, and zinc finger domains of IKKγ were not necessary for the suppressive effect. Furthermore, Hsp70 and IKKγ synergistically suppressed the induction of COX-2 expression by lipopolysaccharides in RAW264.7 cells. These results suggest that overexpression of Hsp70 and IKKγ may be a strategic method for inhibition of NF-κB and related diseases.
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KEYWORD
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COX-2, Hsp70, IKKcomplex, IKKγ, NF-κB
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