Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (263K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (16)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Daniels, P. J.
Right arrow Articles by Andrews, G. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Daniels, P. J.
Right arrow Articles by Andrews, G. K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2002, Vol. 30, No. 14 3130-3140
© 2002 Oxford University Press

Mammalian metal response element-binding transcription factor-1 functions as a zinc sensor in yeast, but not as a sensor of cadmium or oxidative stress

Patrick J. Daniels, Doug Bittel, Irina V. Smirnova, Dennis R. Winge1 and Glen K. Andrews*

Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160-7421, USA and 1 Department of Medicine and Biochemistry, University of Utah Health Sciences Center, Salt Lake City, UT, USA

*To whom correspondence should be addressed. Tel: +1 913 588 6935; Fax: +1 913 588 7035; Email: gandrews{at}kumc.edu
Present addresses:
Doug Bittel, Department of Pediatrics, Children’s Mercy Hospital, Kansas City, MO, USA
Irina V. Smirnova, Department of Physical Therapy, University of Kansas Medical Center, Kansas City, KS 66160-7421, USA

The zinc finger protein, metal response element-binding transcription factor-1 (MTF-1) regulates the expression of genes in response to metal ions and oxidative stress. The precise mechanisms by which this occurs are not understood. To further examine this problem, mouse MTF-1 was expressed in Saccharomyces cerevisiae and tested for the ability to activate metal response element-driven reporter gene expression. Zinc was an effective inducer of reporter gene expression. In general, the magnitude of zinc induction was dependent on the concentration of zinc in the culture medium, but independent of the amount of MTF-1 expression. Zinc induction also occurred with either integrated or episomal reporter plasmids containing the native mouse metallothionein-I proximal promoter. Deletion of fingers 5 and 6 of MTF-1, which function in a zinc-dependent manner to stabilize the DNA-binding activity of the protein in vitro, did not diminish the zinc induction of either episomal or integrated promoters. However, a Gal4 DNA-binding domain– MTF-1 fusion protein, which binds constitutively to the Gal4-responsive promoter, was not zinc inducible but caused constitutive activation of reporter gene expression. This suggests that zinc activation of the DNA-binding activity of MTF-1 is the rate limiting step in its metalloregulatory function in yeast. In contrast, MTF-1 was not responsive to either cadmium or hydrogen peroxide, suggesting that distinct co-activators or signal transduction cascades not found in yeast are required to mediate MTF-1 activation of gene expression by this toxic metal and by oxidative stress.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
K. Kobayashi, J. Kuroda, N. Shibata, T. Hasegawa, Y. Seko, M. Satoh, C. Tohyama, H. Takano, N. Imura, K. Sakabe, et al.
Induction of Metallothionein by Manganese Is Completely Dependent on Interleukin-6 Production
J. Pharmacol. Exp. Ther., February 1, 2007; 320(2): 721 - 727.
[Abstract] [Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
V. Elgazar, V. Razanov, M. Stoltenberg, M. Hershfinkel, M. Huleihel, Y. B. Nitzan, E. Lunenfeld, I. Sekler, and W. F. Silverman
Zinc-regulating Proteins, ZnT-1, and Metallothionein I/II Are Present in Different Cell Populations in the Mouse Testis
J. Histochem. Cytochem., July 1, 2005; 53(7): 905 - 912.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
K. B. Andree, J. Kim, C. P. Kirschke, J. P. Gregg, H. Paik, H. Joung, L. Woodhouse, J. C. King, and L. Huang
Investigation of Lymphocyte Gene Expression for Use as Biomarkers for Zinc Status in Humans
J. Nutr., July 1, 2004; 134(7): 1716 - 1723.
[Abstract] [Full Text]

Home page
 Mol. Cell. Biol.Home page
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]

Home page
 J. Biol. Chem.Home page
H. Jiang, P. J. Daniels, and G. K. Andrews
Putative Zinc-sensing Zinc Fingers of Metal-response Element-binding Transcription Factor-1 Stabilize a Metal-dependent Chromatin Complex on the Endogenous Metallothionein-I Promoter
J. Biol. Chem., August 8, 2003; 278(32): 30394 - 30402.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.