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Heat Shock Inhibits Radiation-induced Activation of NF-κB via Inhibition of I-κB Kinase
Journal article   Open access   Peer reviewed

Heat Shock Inhibits Radiation-induced Activation of NF-κB via Inhibition of I-κB Kinase

Heather A Curry, Regina A Clemens, Sunita Shah, Christopher M Bradbury, Ana Botero, Prabhat Goswami and David Gius
The Journal of biological chemistry, Vol.274(33), pp.23061-23067
08/1999
DOI: 10.1074/jbc.274.33.23061
PMID: 10438474
url
https://doi.org/10.1074/jbc.274.33.23061View
Published (Version of record) Open Access

Abstract

Radiation stimulates signaling cascades that result in the activation of several transcription factors that are believed to play a central role in protective response(s) to ionizing radiation (IR). It is also well established that heat shock alters the regulation of signaling cascades and transcription factors and is a potent radiosensitizing agent. To explore the hypothesis that heat disrupts or alters the regulation of signaling factors activated by IR, the effect of heat shock on IR-induced activation of NF-kappaB was determined. Irradiated HeLa cells demonstrated transient increases in NF-kappaB DNA binding activity and NF-kappaB protein nuclear localization. In addition, irradiated cells demonstrated increased I-kappaB phosphorylation and decreased I-kappaBalpha cytoplasmic protein levels, corresponding temporally with the increase of NF-kappaB DNA binding. Heat shock prior to IR inhibited the increase in NF-kappaB DNA binding activity, nuclear localization of NF-kappaB, and the phosphorylation and subsequent degradation of I-kappaB. I-kappaB kinase (IKK) immunoprecipitation assays demonstrated an increase in IKK catalytic activity in response to IR that was inhibited by pretreatment with heat. Kinetic experiments determined that heat-induced inhibition of NF-kappaB activation in response to IR decayed within 5 h after heating. Furthermore, pretreatment with cycloheximide, to block de novo protein synthesis, did not alter heat shock inhibition of IR induction of NF-kappaB. These experiments demonstrate that heat shock transiently inhibits IR induction of NF-kappaB DNA binding activity by preventing IKK activation and suggests a mechanism independent of protein synthesis.

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