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J.Health Sci., 51(2), 242-247, 2005
Overexpression of Heat Shock Factor 1 Masks the Heavy Metal
Response of the Heat Shock Protein 70
(hsp70) Gene Promoter
Rie Uenishi, Kaoru Suzuki, and Shinji Koizumi*
Department of Health Effects Research, National Institute of Industrial Health, 6-21-1, Nagao, Tama-ku, Kawasaki 214-8585, Japan
Transcription of the heat shock protein 70
(hsp70) gene is induced by heavy metals including Cd and Zn,
probably through the interaction between the heat shock elements (HSE) and heat shock factor 1 (HSF1)
binding to it. We studied the mechanism of this
transcriptional activation by means of electrophoretic
mobility shift assay (EMSA) and transient
transfection assay. In HeLa cells, the DNA-binding activity of
HSF1 was activated by Zn in a
concentration-dependent manner similar to that for
hsp70 gene expression, suggesting the direct contribution of HSF1 to the
metal-induced transcriptional activation. To facilitate the
analysis of the metal-regulatory mechanism, we
attempted to establish a system that can reproduce the
metal activation of overexpressed recombinant HSF1.
In cells transfected with an HSF1 expression vector,
strong HSE-binding activity was detected in EMSA, and reporter gene expression driven by the
hsp70 gene promoter was markedly increased. However, no Zn response was observed in either assay. The overexpressed HSF1 appeared to cause the
constitutive activation of reporter expression, which is an
intriguing feature that might reflect an aspect of the
hsp70 gene regulation.
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