| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 19, 16534-16539, May 11, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Divisions of Transcription of mammalian metallothionein
(MT) genes is activated by heavy metals via multiple copies of a
cis-acting DNA element, the metal-responsive element (MRE).
Our previous studies have shown that certain MREs of the human MT-IIA
gene (MREb, MREc, MREd, and MREf) are less active than the others
(MREa, MREe, and MREg). Gel shift analysis of HeLa cell nuclear
proteins revealed that whereas the active MREs strongly bind the
transcription factor MTF-1 essential for metal regulation, the less
active MREs bind another distinct protein, MREb-BF. This protein
recognizes the GC-rich region of MREb rather than the MRE core required
for MTF-1 binding. All the MREs recognized by MREb-BF contain the CGCCC and/or CACCC motif, suggesting that the MREb-BF·MRE complex contains Sp1 or related proteins. Supershift analysis using antibodies against
Sp1 family proteins as well as gel shift analysis using the recombinant
Sp1 demonstrated that Sp1 represents the majority of MREb-BF activity.
An MREb mutant with reduced affinity to Sp1 mediated
zinc-inducible transcription much more actively than the
wild-type MREb. Furthermore, when placed in the native promoter, this mutant MREb raised the overall promoter activity. These
results strongly suggest that Sp1 acts as a negative regulator of
transcription mediated by specific MREs.
Negative Regulatory Role of Sp1 in Metal Responsive
Element-mediated Transcriptional Activation*
§,,
,
Hazard Assessment and
¶ Health Effects Research, National Institute of Industrial
Health, 6-21-1, Nagao, Tama-ku, Kawasaki 214-8585 and the ** Department
of Environmental Toxicology, Faculty of Pharmaceutical Sciences, Teikyo
University, Sagamiko, Kanagawa 199-0195, Japan
*
This work was supported in part by a grant-in-aid from the
Science and Technology Agency, Japan.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Dept. of Molecular Genetics, Alton Ochsner
Medical Foundation, 1516 Jefferson Highway, New Orleans, LA 70121.
To whom correspondence should be addressed. Tel.:
81-44-865-6111; Fax: 81-44-865-6116; E-mail: koizumi@niih.go.jp.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Li, T. Kimura, R. W. Huyck, J. H. Laity, and G. K. Andrews Zinc-Induced Formation of a Coactivator Complex Containing the Zinc-Sensing Transcription Factor MTF-1, p300/CBP, and Sp1 Mol. Cell. Biol., July 1, 2008; 28(13): 4275 - 4284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Taheri and H. E. P. Bazan Platelet-Activating Factor Overturns the Transcriptional Repressor Disposition of Sp1 in the Expression of MMP-9 in Human Corneal Epithelial Cells Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 1931 - 1941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. K. Steagall, J.-P. Lin, and J. Moss The C/A(-18) polymorphism in the surfactant protein B gene influences transcription and protein levels of surfactant protein B Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L448 - L453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, T. Kimura, J. H. Laity, and G. K. Andrews The Zinc-Sensing Mechanism of Mouse MTF-1 Involves Linker Peptides between the Zinc Fingers Mol. Cell. Biol., August 1, 2006; 26(15): 5580 - 5587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-A. Lee, D.-C. Suh, J.-E. Kang, M.-H. Kim, H. Park, M.-N. Lee, J.-M. Kim, B.-N. Jeon, H.-E. Roh, M.-Y. Yu, et al. Transcriptional Activity of Sp1 Is Regulated by Molecular Interactions between the Zinc Finger DNA Binding Domain and the Inhibitory Domain with Corepressors, and This Interaction Is Modulated by MEK J. Biol. Chem., July 29, 2005; 280(30): 28061 - 28071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-C. Chou, H.-Y. Chen, S.-L. Yu, L. Cheng, P.-C. Yang, and C. V. Dang Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation Blood, July 1, 2005; 106(1): 304 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Rutherford and A. J. Bird Metal-Responsive Transcription Factors That Regulate Iron, Zinc, and Copper Homeostasis in Eukaryotic Cells Eukaryot. Cell, February 1, 2004; 3(1): 1 - 13. [Full Text] [PDF]
|
|
|
|
|
|
B. Zhang, O. Georgiev, M. Hagmann, C. Gunes, M. Cramer, P. Faller, M. Vasak, and W. Schaffner Activity of Metal-Responsive Transcription Factor 1 by Toxic Heavy Metals and H2O2 In Vitro Is Modulated by Metallothionein Mol. Cell. Biol., December 1, 2003; 23(23): 8471 - 8485. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Faraco, P. Giardina, and G. Sannia Metal-responsive elements in Pleurotus ostreatus laccase gene promoters Microbiology, August 1, 2003; 149(8): 2155 - 2162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang, S. Wang, R. A. Wesley, and R. L. Danner Adjacent Sequence Controls the Response Polarity of Nitric Oxide-sensitive Sp Factor Binding Sites J. Biol. Chem., August 1, 2003; 278(31): 29192 - 29200. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
