Differential control of the metal-mediated activation of the human heme oxygenase-1 and metallothionein IIA genes.
Heme oxygenase-1, an essential enzyme in heme catabolism, and metallothionein IIA, a small metal-binding protein with clusters of cysteins, are remarkably induced in HeLa cells following the treatment with cadmium or zinc. Both proteins are considered to be involved in the defense system against metal toxicity. Here we showed by transient expression assays that the cadmium-responsive element (CdRE) of the human heme oxygenase-1 gene is not responsive to zinc, whereas a metal-regulatory element (MRE) of the human metallothionein IIA gene is able to respond to either cadmium or zinc. The CdRE is recognized by a certain nuclear protein(s) which is however unable to bind to an MRE of the metallothionein IIA gene. These results suggest that the metal-selective activation of each gene promoter is mediated by a separate mechanism.
Takeda
K
K
Department of Applied Physiology and Molecular Biology, Tohoku University School of Medicine, Miyagi, Japan.
Fujita
H
H
Shibahara
S
S
D001483:Base Sequence; D002104:Cadmium / Q000494:pharmacology*; D019256:Cadmium Chloride; D002712:Chlorides / Q000494:pharmacology*; D016384:Consensus Sequence; D004790:Enzyme Induction; D005786:Gene Expression Regulation / Q000187:drug effects*; D006367:HeLa Cells; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D006801:Humans; D008668:Metallothionein / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D010957:Plasmids; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D017967:Zinc Compounds / Q000494:pharmacology*
D002712:Chlorides; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D017967:Zinc Compounds; D002104:Cadmium; C016837:zinc chloride; D008668:Metallothionein; D006419:Heme Oxygenase (Decyclizing); D019256:Cadmium Chloride