PMID- 15378601
OWN - NLM
STAT- MEDLINE
DCOM- 20050318
LR  - 20231213
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 93
IP  - 3
DP  - 2004 Oct 15
TI  - C-terminal deletion mutant of MRE-binding transcription factor-1 inhibits 
      MRE-driven gene expression.
PG  - 609-18
AB  - Heavy metal-induced transcriptional activation of the genes coding for 
      metallothionein (MT) is mediated by a cis-acting DNA element, the 
      metal-responsive element (MRE). MRE-binding transcription factor-1 (MTF-1) is a 
      highly conserved heavy metal-induced transcriptional activator. MTF-1 also 
      activates transcription in response to oxidative stress and regulates the 
      expression of several cytoprotective factor genes, including MT, 
      gamma-glutamylcysteine synthetase, and Cu/Zn-superoxide dismutase. It is thus 
      thought that MTF-1 plays a role in cellular stress response. The physiological 
      role of MTF-1 remains unclear because of the lack of MTF-1-specific activators 
      and/or inhibitors. To obtain an MTF-1-specific inhibitor, we constructed an 
      MTFDeltaC (amino acids 1-317), a C-terminal deletion mutant of MTF-1. MTFDeltaC 
      could bind MRE and competed with MTF-1 for MTF-MRE complex formation. Transient 
      expression of MTFDeltaC in HepG2 cells reduced MRE-driven gene expression, 
      demonstrating that MTFDeltaC is dominant to MTF-1. HepG2 cells stably expressing 
      MTFDeltaC showed increased susceptibility to the cytotoxic effects of tert-butyl 
      hydroperoxide (tBH). Furthermore, we constructed Ad5MTFDeltaC, a recombinant 
      adenovirus that expresses MTFDeltaC. Infection with the virus induced MTFDeltaC 
      expression and increased susceptibility to the cytotoxic effects of tBH. These 
      results indicate that MTF-1 participates in controlling the cellular redox state.
CI  - Copyright 2004 Wiley-Liss, Inc.
FAU - Kimura, Tomoki
AU  - Kimura T
AD  - Department of Toxicology, Faculty of Pharmaceutical Sciences, Setsunan 
      University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan. 
      tomoki@pharm.setsunan.ac.jp
FAU - Itoh, Norio
AU  - Itoh N
FAU - Sone, Tomomichi
AU  - Sone T
FAU - Tanaka, Keiichi
AU  - Tanaka K
FAU - Isobe, Masakazu
AU  - Isobe M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Transcription Factors)
RN  - 9038-94-2 (Metallothionein)
RN  - 955VYL842B (tert-Butylhydroperoxide)
SB  - IM
MH  - DNA-Binding Proteins
MH  - Electrophoretic Mobility Shift Assay
MH  - Gene Expression Regulation, Neoplastic/drug effects/*genetics
MH  - Genes, Reporter/genetics
MH  - Humans
MH  - Metallothionein/genetics/metabolism
MH  - Mutation/*genetics
MH  - Promoter Regions, Genetic/genetics
MH  - Regulatory Sequences, Nucleic Acid/*genetics
MH  - Transcription Factors/genetics/*metabolism
MH  - Tumor Cells, Cultured
MH  - tert-Butylhydroperoxide/toxicity
MH  - Transcription Factor MTF-1
EDAT- 2004/09/21 05:00
MHDA- 2005/03/19 09:00
CRDT- 2004/09/21 05:00
PHST- 2004/09/21 05:00 [pubmed]
PHST- 2005/03/19 09:00 [medline]
PHST- 2004/09/21 05:00 [entrez]
AID - 10.1002/jcb.20210 [doi]
PST - ppublish
SO  - J Cell Biochem. 2004 Oct 15;93(3):609-18. doi: 10.1002/jcb.20210.