金屬感應轉錄因子為具六個C2H2類型鋅指結構之轉錄因子，它能調控金屬硫蛋白基因基礎表現以及受金屬刺激後之表現。目前已知若干逆境，如鋅離子，會促使金屬感應轉錄因子進入細胞核中而執行其功能，然引導其進核之進核信號與進核機制尚未明朗。在我們的實驗中，將不同金屬感應轉錄因子片段與綠螢光蛋白形成融合蛋白，並利用螢光顯微鏡觀察各片段於細胞內分佈之情形。金屬感應轉錄因子六個鋅指結構具有受鋅離子誘導進入細胞核之能力，其中單獨第四個鋅指結構便能進入細胞核中。利用GST pull-down assay，我們發現金屬感應轉錄因子能與各類型的importin α結合，且單獨第三或第四個鋅指結構便可和α1結合。此外，我們證實金屬感應轉錄因子第四個鋅指結構內，仳鄰構成鋅指結構之第一個組氨酸的兩個鹼性胺基酸殘基不但會影響金屬感應轉錄因子進核的作用，同時也影響其與importin α之結合能力。我們另外將金屬感應轉錄因子前端之典型進核信號與六個鋅指結構形成融合蛋白，並發現此融合蛋白進入細胞核之能力遠勝於單獨六個鋅指結構者。綜觀上述，我們推測調控金屬感應轉錄因子受鋅離子刺激進入細胞核之進核信號位於鋅指結構內，尤以第四個鋅指結構為要，其前端之典型進核信號能夠加強金屬感應轉錄因子進核之能力；且金屬感應轉錄因子之進核需要importin α協助才能完成。

Metal responsive transcription factor 1 (MTF-1) is a transcription factor that contains six C2H2 zinc fingers, and is essential for the basal and zinc-inducing expression of metallothionein. It was shown previously that the nuclear entry of MTF-1 could be induced by zinc. However, the region serving as nuclear localization signal (NLS) and nuclear import mechanism remain unclear. Here we generated a series of eGFP-tagged deletion mutants of MTF-1 and investigated the subcellular localization of these fusion proteins by fluorescence microscopy. We found that zinc finger domain of MTF-1 might contain an NLS. Using GST pull-down assay, we were able to demonstrate that MTF-1 binds to a variety of importin α families. Further analysis of the individual zinc finger showed that only zinc finger 3 and 4 bound importin α1. We also found that R246 and K247 adjacent to the first constituent His of MTF-1 zinc finger 4 are crucial for the nuclear transport of MTF-1 since mutation of these sites impaired the function of nuclear translocation of MTF-1 and its binding ability to importin α1. Furthermore, fusion protein of 6 zinc fingers with the classical NLS ahead of the zinc finger showed a better nuclear import than 6 zinc fingers alone. Overall, our results indicate that nuclear entry of MTF-1 after zinc induction is mediated by the NLS within the zinc finger domain. Among which, zinc finger 4 plays the most important role. Besides, the classical NLS adjacent to zinc finger domain enhances the nuclear translocation. Presence of either importin family is required for the translocation of MTF-1.

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