MTF-1 (metal-responsive transcription factor 1) is an essential mammalian protein for embryonic development and modulates the expression of genes involving in zinc homoeostasis and responding to oxidative stress. We report in the present paper that PTEN (phosphatase and tensin homologue deleted on chromosome 10) associates with MTF-1 in the cells. These two proteins interact via the acidic domain of MTF-1 and the phosphatase/C2 domain of PTEN. Depletion of PTEN reduced MT (metallothionein) gene expression and increased cellular sensitivity to cadmium toxicity. PTEN did not alter the nuclear translocation, protein stability or DNA-binding activity of MTF-1. Zinc increased MTF-1–PTEN interaction in a dose-dependent manner. The interaction elevated within 2 h of zinc addition and declined afterwards in the cells. The enhanced binding activity occurred mainly in the cytoplasm and reduced after translocating the MTF-1 into the nucleus. Blocking signalling through the PI3K (phosphoinositide 3-kinase) pathway did not alter the zinc-induced MT expression. Analysis of enzymatically inactive PTEN mutants demonstrated that protein but not lipid phosphatase activity of PTEN was involved in the regulation of MTF-1 activity. The same regulatory role of PTEN was also noted in the regulation of ZnT1 (zinc transporter 1), another target gene of MTF-1.
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Research Article|
December 14 2011
PTEN interacts with metal-responsive transcription factor 1 and stimulates its transcriptional activity
Meng-Chieh Lin;
Meng-Chieh Lin
*Department of Life Science and Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan
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Ya-Chuan Liu;
Ya-Chuan Liu
*Department of Life Science and Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan
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Ming F. Tam;
Ming F. Tam
†Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan
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Yu-Ju Lu;
Yu-Ju Lu
*Department of Life Science and Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan
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Ya-Ting Hsieh;
Ya-Ting Hsieh
*Department of Life Science and Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan
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Lih-Yuan Lin
Lih-Yuan Lin
1
*Department of Life Science and Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan
1To whom correspondence should be addressed (email lylin@life.nthu.edu.tw).
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Publisher: Portland Press Ltd
Received:
July 13 2011
Revision Received:
August 10 2011
Accepted:
September 01 2011
Accepted Manuscript online:
September 01 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem J (2012) 441 (1): 367–377.
Article history
Received:
July 13 2011
Revision Received:
August 10 2011
Accepted:
September 01 2011
Accepted Manuscript online:
September 01 2011
Citation
Meng-Chieh Lin, Ya-Chuan Liu, Ming F. Tam, Yu-Ju Lu, Ya-Ting Hsieh, Lih-Yuan Lin; PTEN interacts with metal-responsive transcription factor 1 and stimulates its transcriptional activity. Biochem J 1 January 2012; 441 (1): 367–377. doi: https://doi.org/10.1042/BJ20111257
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