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PMID: 8467794 Published · ppublish English Journal Article

Cloned transcription factor MTF-1 activates the mouse metallothionein I promoter.

The EMBO journal ·Vol. 12 ·No. 4 ·1993-04-00 ·Pages 1355-62

Radtke F, Heuchel R, Georgiev O, Hergersberg M, Gariglio M, Dembic Z, Schaffner W

Abstract

Metallothioneins (MTs) are small cysteine-rich proteins whose structure is conserved from fungi to man. MTs strongly bind heavy metals, notably zinc, copper and cadmium. Upon exposure of cells to heavy metal and other adverse treatments, MT gene transcription is strongly enhanced. Metal induction is mediated by several copies of a 15 bp consensus sequence (metal-responsive element, MRE) present in the promoter region of MT genes. We and others have demonstrated the presence of an MRE-binding factor in HeLa cell nuclear extracts. We found that this factor, termed MTF-1 (MRE-binding transcription factor) is inactivated/reactivated in vitro by zinc withdrawal/addition. Here we report that the amounts of MTF-1-DNA complexes are elevated several-fold in zinc-treated cells, as measured by bandshift assay. We have also cloned the cDNA of mouse MTF-1, a 72.5 kDa protein. MTF-1 contains six zinc fingers and separate transcriptional activation domains with high contents of acidic and proline residues. Ectopic expression of MTF-1 in primate or rodent cells strongly enhances transcription of a reporter gene that is driven by four consensus MREd sites, or by the complete mouse MT-I promoter, even at normal zinc levels.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Cell Line Cloning, Molecular DNA-Binding Proteins/genetics Gene Expression Metallothionein/genetics Mice Molecular Sequence Data Oligodeoxyribonucleotides/chemistry,metabolism Promoter Regions, Genetic RNA, Messenger/genetics Recombinant Proteins/metabolism Transcription Factors/genetics Zinc/physiology Zinc Fingers
Chemicals
DNA-Binding Proteins Oligodeoxyribonucleotides RNA, Messenger Recombinant Proteins Transcription Factors transcription factor MTF-1 Metallothionein Zinc
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Radtke F
Universität Zürich, Institut für Molekularbiologie II, Switzerland.
Heuchel R
Georgiev O
Hergersberg M
Gariglio M
Dembic Z
Schaffner W
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1993-04-00
Pages
1355-62
Language
English
Region
England
NLM ID
8208664
PMCID
PMC413347
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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