SUMO是small ubiquitin-like modifier，而Daxx是Fas death-domain association protein，在一般的情況之下，SUMO與Daxx主要是存在於核內的。將SUMO與紅色螢光蛋白形成融合蛋白送進細胞中，active SUMO（可進行sumoylatoin）會進核內並形成nuclear bodies，而inactive SUMO（無sumoylation的能力）會散佈在細胞質中。Daxx是SUMO的目標蛋白之一，也是組成POD的蛋白，當有外界的壓力且有Ask1存在之下，Daxx會跑到細胞質中，因此，Daxx應該是一個shuttle protein，它應該擁有nuclear localization signal（NLS）以及nuclear export signal（NES）。為了確認Daxx的NES和NLS motif，將Daxx分為四段：D1、D2、D3和D4，另外將預測為NES和NLS motif的氨基酸進行突變。在顯微鏡下可以觀察到，D1（包含NES motif）以及D4（包含NLS2 motif）可以進入核內，但若是NES或NLS2 motif的突變則會阻斷Daxx的入核，NES及NLS2 motif都與Daxx的nuclear transport有關。不過，若是active SUMO與突變的Daxx或是inactive SUMO與wild type Daxx一起送入細胞內，則可以觀察到無法入核的SUMO或Daxx會被攜帶入核內。因此， SUMO似乎是藉由interaction或sumoylation把突變的Daxx帶入核內，而Daxx似乎也可以藉由interaction將inactive SUMO帶入核內，所以active SUMO及Daxx似乎都會扮演著nuclear transporter的角色。

SUMO is a small ubiquitin-like modifier. The fluorescent fused SUMO (active for sumoylation) localized in the nucleus, while C-terminal truncated SUMO (inactive for sumoylation) diffused in the cytoplasm. Daxx is a SUMO target protein, locates predominantly in the nucleus. It has been identified as a component of the PODs. During extracellular stimulation, Daxx could be recruited to the cytoplasm with the existence of Ask1. Therefore, it is a shuttle protein. Daxx should contain nuclear localization signal (NLS) and nuclear export signal (NES) motifs. To identify the NES and NLS motifs on Daxx, Daxx were truncated into four segments. Several amino acids on the predicted NES and NLS motifs were mutated. Our results showed that the truncated Daxx fragments D1 (containing NES) and D4 (containing NLS2) could be translocated into nucleus independently. However, either NES or NLS2 mutants disrupted their translocation into nucleus. It indicated that both NES and NLS2 motif of Daxx were involved in the nuclear transport. Nevertheless the co-transfection of SUMOs and Daxx showed that the interactions between SUMO active form and Daxx mutants and between inactive SUMO and Daxx wild type rescued the nuclear transport function of Daxx mutants and inactive SUMO. Therefore, SUMO may play a role in the nuclear transport of Daxx by either sumoylation or interaction with Daxx in cytoplasm, and Daxx may recruit inactive SUMOs into nucleus by interaction.

中文摘要……………………………………………………………………I
英文摘要…………………………………………………………………..II
縮寫表……….……………………………………………………………III
壹、 緒論…………………………………………………………………..2
1、 Daxx………………………………………………………………....2
1.1 Daxx的基因構造 (gene structure).................…………................2
1.2 Daxx的蛋白質構造 (protein structure)………………………..2
1.3 Daxx在細胞中的角色 (Cellular function)….…………………4
1.3.1 Daxx與細胞凋亡的關係..…………………………………..4
1.3.1.1 Fas/Ask1 pathway………………………………………....4
1.3.1.2轉形生長因子(TGF)-

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