ACLS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Liang, R.
Right arrow Articles by Shiao, Y.-H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liang, R.
Right arrow Articles by Shiao, Y.-H.
Annals of Clinical & Laboratory Science 31:91-98 (2001)
© 2001 Association of Clinical Scientists

Presence of Potential Nickel-Responsive Element(s) in the Mouse MTH1 Promoter

Rongti Liang1, Hisato Igarashi2, Teruhisa Tsuzuki3, Yusaku Nakabeppu2,4, Mutsuo Sekiguchi5, Kazimierz S. Kasprzak1 and Yih-Horng Shiao1
1 Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, Maryland, USA
2 Department of Biochemistry, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
3 Department of Medical Biophysics and Radiation Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
4 CREST, Japan Science and Technology Corporation, Sawara-Ku, Fukuoka, Japan
5 Department of Biology and Frontier Research Center, Fukuoka Dental College, Fukuoka, Japan

Address correspondence to Yih-Horng Shiao, Ph.D., Building 538, Room 205, NCI-Frederick, Frederick, MD 21702, USA; tel 301 846 1246; fax 301 846 5946; e-mail shiao{at}mail.ncifcrf.gov.

The murine MTH1 gene codes for MTH1, an 8-oxo-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase (8-oxo-dGTPase) which hydrolyzes 8-oxo-dGTP, a promutagenic product of reactive oxygen species’ attack on the nucleotide pool. This gene is regulated by oxidative stress. Therefore, we hypothesized that MTH1 expression can be affected by carcinogenic nickel(II), known to induce such stress. Three plasmid constructs, carrying different upstream regions of the mouse MTH1 and the chloramphenicol acetyltransferase (CAT) reporter gene, were transiently transfected into NIH 3T3 cells and the CAT protein was measured in nickel(II) acetate-treated and untreated cells. Nickel concentration-dependent increase of CAT protein level was observed for low Ni(II) concentrations, up to 400 µM Ni(II), in cells transfected with pHI103 plasmid (-5969 to +530 of the MTH1 sequence) only. Cells transfected with the pHI104 (-1331 to +530) or pHI108 (-151 to +530) plasmids did not respond to nickel(II) whatsoever. This finding demonstrated that the MTH1 sequence between -5969 and -1331 contained element(s) responsive to nickel(II) treatment. DNA sequencing revealed the presence of AP-1, NF-{kappa}B, and ATF-1 binding sites in both the -5969 to -1331 and -1331 to +530 regions. In contrast, two (CA)n repeats (-5642 to -5582 and -2078 to -2031), a family of B2 (-5428 to -5247) and B1 (-4559 to -4420) short interspersed repeated elements, and an (AT)n repeat (-5243 to -5230) were identified only in the -5969 to -1331 sequence. The results suggest that up-regulation of murine MTH1 expression by nickel(II) is controlled by the repeat sequences, potential candidates for nickel-responsive elements.

Keywords: nickel, MTH1 gene, promoter, responsive element, gene expression




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
H. Pang, M. Bartlam, Q. Zeng, H. Miyatake, T. Hisano, K. Miki, L.-L. Wong, G. F. Gao, and Z. Rao
Crystal Structure of Human Pirin: AN IRON-BINDING NUCLEAR PROTEIN AND TRANSCRIPTION COFACTOR
J. Biol. Chem., January 9, 2004; 279(2): 1491 - 1498.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2001 by the Association of Clinical Scientists.