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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-28747

Lindert, U; Cramer, M; Meuli, M; Georgiev, O; Schaffner, W (2009). Metal-responsive transcription factor 1 (MTF-1) activity is regulated by a nonconventional nuclear localization signal and a metal-responsive transactivation domain. Molecular and Cellular Biology, 29(23):6283-6293.

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Metal-responsive transcription factor 1 (MTF-1) mediates both basal and heavy metal-induced transcription of metallothionein genes and also regulates other genes involved in the cell stress response and in metal homeostasis. In resting cells, MTF-1 localizes to both the cytoplasm and the nucleus but quantitatively accumulates in the nucleus upon metal load and under other stress conditions. Here we show that within the DNA-binding domain, a region spanning zinc fingers 1 to 3 (amino acids [aa] 137 to 228 in human MTF-1) harbors a nonconventional nuclear localization signal. This protein segment confers constitutive nuclear localization to a cytoplasmic marker protein. The deletion of the three zinc fingers impairs nuclear localization. The export of MTF-1 to the cytoplasm is controlled by a classical nuclear export signal (NES) embedded in the acidic activation domain. We show that this activation domain confers metal inducibility in distinct cell types when fused to a heterologous DNA-binding domain. Furthermore, the cause of a previously described stronger inducibility of human versus mouse MTF-1 could be narrowed down to a 3-aa difference in the NES; "humanizing" mouse MTF-1 at these three positions enhanced its metal inducibility to the level of human MTF-1.


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Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Date:December 2009
Deposited On:09 Feb 2010 18:30
Last Modified:05 Apr 2016 13:49
Publisher:American Society for Microbiology
Publisher DOI:10.1128/MCB.00847-09
PubMed ID:19797083

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