NDLI: Cadmium-responsive Element of the Human Heme Oxygenase-1 Gene Mediates Heat Shock Factor 1-dependent Transcriptional Activation

Content Provider	Journal of Biological Chemistry (JBC)
Author	Koizumi, Shinji Gong, Pengfei Suzuki, Kaoru Murata, Mie
Abstract	Transcription of a number of mammalian genes is activated by heavy metals, but mechanisms of signaling and transcriptional regulation are not well understood. From a comparison of heavy metal responses of several human genes, it was noted that the heme oxygenase-1 (HO-1) gene is quite similar in the spectrum of metal response and induction kinetics to the heat shock protein 70 (HSP70) gene, suggesting a common regulatory mechanism shared by these genes. The cadmium-responsive element (CdRE) known to be responsible for the metal regulation of ho-1 formed complexes with proteins from heavy metal-treated HeLa cells in an electrophoretic mobility shift assay (EMSA). These complexes were indistinguishable in mobility from those formed by the heat shock factor 1 (HSF1) and the heat shock element involved in hsp70 regulation, suggesting the involvement of HSF1 also in the CdRE complexes. Competitive EMSA and supershift analysis with an anti-HSF1 antibody revealed that HSF1 was in fact a component of the CdRE complexes. A fine analysis on the affinity of HSF1 to a series of mutant CdRE sequences showed that HSF1 recognizes a sequence motif TnCTAGA. Transient transfection analysis with overexpressed recombinant HSF1 demonstrated that CdRE has HSF1-dependent enhancer-like activity that requires direct binding of HSF1. In the absence of overexpressed HSF1, however, CdRE by itself was insufficient to mediate heavy metal-induced transcription, suggesting requirement of additional regulatory sequences. The finding that HSF1 is directly involved in the regulation of ho-1 with an anti-oxidative role revealed a new aspect of the biological defense mechanism.
Related Links	http://www.jbc.org/content/282/12/8715.abstract
Ending Page	8723
Starting Page	8715
Page Count	9
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	12
Volume Number	282
DOI	10.1074/jbc.M609427200
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2007-03-23
Access Restriction	Open
Subject Keyword	Genes: Structure and Regulation
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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