S-Space College of Medicine/School of Medicine (의과대학/대학원) Immunology (면역학전공) Journal Papers (저널논문_면역학전공)
Heat shock protein 70 negatively regulates the heat-shock-induced suppression of the IkappaB/NF-kappaB cascade by facilitating IkappaB kinase renaturation and blocking its further denaturation
- Lee, K. H.; Lee, C. T.; Kim, Y. W.; Han, S. K.; Shim, Y. S.; Yoo, C. G.
- Issue Date
- Exp Cell Res. 2005 Jul 1;307(1):276-84. Epub 2005 Apr 13.
- Adenoviridae/genetics; Blotting, Western; Bronchi/cytology; Cell Culture Techniques; Cell Line; Electrophoretic Mobility Shift Assay; Enzyme Activation; Epithelial Cells/cytology; Gene Expression Regulation/drug effects/*genetics; HSP70 Heat-Shock Proteins/biosynthesis/metabolism; Heat-Shock Response/drug effects/*genetics; Hot Temperature; Humans; I-kappa B Proteins/*metabolism; NF-kappa B/genetics/*metabolism/pharmacology; *Protein Renaturation; Recombinant Proteins/metabolism/pharmacology; Time Factors; Transduction, Genetic; Up-Regulation
- Heat shock (HS) treatment has been previously shown to suppress the IkappaB/nuclear factor-kappaB (NF-kappaB) cascade by denaturing, and thus inactivating IkappaB kinase (IKK). HS is characterized by the induction of a group of heat shock proteins (HSPs). However, their role in the HS-induced suppression of the IkappaB/NF-kappaB cascade is unclear. Adenovirus-mediated HSP70 overexpression was found not to suppress the TNF-alpha-induced activation of the IkappaB/NF-kappaB pathway, thus suggesting that HSP70 is unlikely to suppress this pathway. When TNF-alpha-induced activation of the IkappaB/NF-kappaB pathway was regained 24 h after HS, HSP70 was found to be highly up-regulated. Moreover, blocking HSP70 induction delayed TNF-alpha-induced IkappaBalpha degradation and the resolubilization of IKK. In addition, HSP70 associated physically with IKK, suggesting that HSP70 is involved in the recovery process via molecular chaperone effect. Adenovirus-mediated HSP70 overexpression prior to HS blocked the IkappaBalpha stabilizing effect of HS by suppressing IKK insolubilization. Moreover, the up-regulation of endogenous HSP70 by preheating, suppressed this subsequent HS-induced IKK insolubilization, and this effect was abrogated by blocking HSP70 induction. These findings indicate that HSP70 accumulates during HS and negatively regulates the HS-induced suppression of the IkappaB/NF-kappaB cascade by facilitating the renaturation of IKK and blocking its further denaturation.
- 0014-4827 (Print)
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