| First Author | Lindert U | Year | 2009 |
| Journal | Mol Cell Biol | Volume | 29 |
| Issue | 23 | Pages | 6283-93 |
| PubMed ID | 19797083 | Mgi Jnum | J:154996 |
| Mgi Id | MGI:4412128 | Doi | 10.1128/MCB.00847-09 |
| Citation | Lindert U, et al. (2009) Metal-responsive transcription factor 1 (MTF-1) activity is regulated by a nonconventional nuclear localization signal and a metal-responsive transactivation domain. Mol Cell Biol 29(23):6283-93 |
| abstractText | 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. |
