Back to Search
Start Over
A Novel Cysteine Cluster in Human Metal-responsive Transcription Factor 1 Is Required for Heavy Metal-induced Transcriptional Activation in Vivo.
- Source :
-
Journal of Biological Chemistry . 2/6/2004, Vol. 279 Issue 6, p4515-4522. 8p. 4 Black and White Photographs, 3 Diagrams, 2 Graphs. - Publication Year :
- 2004
-
Abstract
- Metal-responsive transcription factor 1 (MTF-1) specifically binds to metal response elements (MREs) associated with a number of metal- and stress-responsive genes. Human MTF-1 contains a cysteine-rich cluster, -632Cys-Gln-Cys-Gln-Cys-Ala-Cys638-, conserved from pufferfish to humans far removed from the MRE-binding zinc finger domain and just C-terminal to a previously mapped serine/threonine-rich transcriptional activation domain. MTF-1 proteins containing two Cys→Ala substitutions (C632A/C634A) or a deletion in this region altogether (Δ(632-644)) are significantly impaired in their ability to induce Zn(II)- and Cd(II)-responsive transcription of a MRE-linked reporter gene in transiently transfected mouse dko7 (MTF-1-/-) cells in culture under moderate metal stress but retain the ability to drive basal levels of transcription in a MRE-dependent manner in vivo and in vitro. In addition, the mutated proteins respond to induction by Zn(II) or Cd(II) with nuclear translocation and MRE binding activities comparable with wild-type MTF-1. Attempts to rescue the Δ(632-644) deletion mutant phenotype by insetting similar Cys-rich sequences from Drosophila MTF-1 were unsuccessful, suggesting that the structure of this motif within intact human MTF-1, rather than the simple presence of multiple closely spaced Cys residues, is required for function. This cysteine cluster therefore functions at a step subsequent to nuclear translocation and MRE-binding DNA to naked promoter-containing DNA and appears to be specifically required for MTF-1 to activate transcription in the presence of inducing heavy metal ions. [ABSTRACT FROM AUTHOR]
- Subjects :
- *TRANSCRIPTION factors
*GENES
*PROTEINS
*BIOCHEMISTRY
*BIOLOGY
*CHEMISTRY
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 279
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 12507304
- Full Text :
- https://doi.org/10.1074/jbc.M308924200