title: Cross talk of heat shock and heavy metal regulatory pathways.
abstract: Heavy metals induce transcription of human genes including those coding for metallothionein and heat shock protein 70 (HSP70). It has been suggested that these processes are mediated by metal-activated transcription factors, MTF-1 and HSF1, respectively, and are independent of each other. We raised an antibody against human MTF-1 which efficiently supershifts the protein-DNA complex formed by MTF-1 and its cognate binding sequence, MRE. We discovered that this antibody could also supershift complexes formed by HSF1 and its recognition sequence HSE, which suggested the involvement of MTF-1 in these complexes. This supershift was observed for HSF1/HSE complexes induced by Zn, Cd, Ag, and heat shock. Furthermore, overexpression of MTF-1 in HeLa cells markedly reduced metal-induced transcription from the hsp70-1 gene promoter which depends on HSF1. These data indicate that MTF-1 represses HSF1-mediated transcription probably through a direct protein-protein interaction, suggesting a cross talk of two lines of stress-responsive regulatory pathways.
authors.affiliation: Department of Health Effects Research, National Institute of Industrial Health, 6-21-1 Nagao, Tama-ku, Kawasaki 214-8585, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Uenishi
authors.forename: Pengfei
authors.initials: P
authors.lastname: Gong
authors.forename: Kaoru
authors.initials: K
authors.lastname: Suzuki
authors.forename: Shinji
authors.initials: S
authors.lastname: Koizumi
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006801:Humans; D012834:Silver / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology; D000097809:Transcription Factor MTF-1
chemical_list: D000906:Antibodies; D002104:Cadmium; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D012834:Silver; D014157:Transcription Factors; D015032:Zinc; D000097809:Transcription Factor MTF-1; C000619706:HSF1 protein, human