Heat shock protein 70 negatively regulates the heat-shock-induced suppression of the I{kappa}B/NF-{kappa}B cascade by facilitating I{kappa}B kinase renaturation and blocking its further denaturation

Journal Article · Fri Jul 01 04:00:00 EDT 2005 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2005.03.014· OSTI ID:20717624

Lee, Kyoung-Hee; Lee, Choon-Taek; Kim, Young Whan ^[1]; Han, Sung Koo ^[1]; Shim, Young-Soo ^[1]; Yoo, Chul-Gyu ^[1]

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1. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of)

Heat shock (HS) treatment has been previously shown to suppress the I{kappa}B/nuclear factor-{kappa}B (NF-{kappa}B) cascade by denaturing, and thus inactivating I{kappa}B 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 I{kappa}B/NF-{kappa}B cascade is unclear. Adenovirus-mediated HSP70 overexpression was found not to suppress the TNF-{alpha}-induced activation of the I{kappa}B/NF-{kappa}B pathway, thus suggesting that HSP70 is unlikely to suppress this pathway. When TNF-{alpha}-induced activation of the I{kappa}B/NF-{kappa}B pathway was regained 24 h after HS, HSP70 was found to be highly up-regulated. Moreover, blocking HSP70 induction delayed TNF-{alpha}-induced I{kappa}B{alpha} 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 I{kappa}B{alpha} 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 I{kappa}B/NF-{kappa}B cascade by facilitating the renaturation of IKK and blocking its further denaturation.

• OSTI ID: 20717624
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 307; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADENOVIRUS
GENE REGULATION
HEAT TREATMENTS
HEAT-SHOCK PROTEINS
INHIBITION