中文摘要
金屬感應轉錄因子(MTF-1)受到重金屬刺激、環境逆境而活化。一般情況下大多數的金屬感應轉錄因子處於細胞質，而受到刺激時進入會細胞核並表現下游基因。轉譯後修飾作用可能影響蛋白質活性、細胞中分佈或蛋白質交互作用，然而不同的刺激可能影響不同的轉譯後修飾作用。金屬感應轉錄因子會受到小泛素修飾，鋅的刺激會使SUMO-1修飾程度下降。在本實驗中我們發現砷的刺激使金屬感應轉錄因子也使得小泛素修飾程度下降，並證明小泛素修飾位置也是在Lysine 627位置，小泛素修飾程度下降的情形會因為SIM序列突變而消失。我們也證明金屬感應轉錄因子受到砷刺激會有快速進入細胞核再由細胞核返回細胞質的情形，利用Lysine 627突變證明修飾的小泛素並不影響此進出細胞核的情形，但影響下游基因的表現量；大量表現SENP2發現金屬感應轉錄因子受到砷刺激會與未知蛋白質進行交互作用，並且此未知蛋白會受到SUMO-3修飾，在相同情況下金屬感應轉錄因子受到砷刺激而離開核情形消失，並且累積在細胞核中，累積在細胞核的現象也反應在金屬感應轉錄因子SIM序列的缺失時。我們發現砷刺激使金屬轉錄因子改變在細胞中的分布，並利用降低SUMO修飾程度來增加表現下游基因的表現量，其作用與鋅處理截然不同。

Abstract
Metal-responsive transcription factor 1 (MTF-1) mainly resided in the cytoplasm. Upon stimulation, it translocated into nucleus and activates gene expression. Post-translational modifications involved in different cellular processes, such as transcriptional regulation, nuclear-cytosolic transport, and protein-protein interaction. Previously, we observed that mouse MTF-1 can be modified by both SUMO-1 (small ubiquitin-like modifier 1) and SUMO-3 on lysine 627 residue. The level of sumoylation was reduced by zinc treatment in both dose- and time-dependent manners. Here we demonstrated that the level of sumoylation was also reduced by arsenic treatment. The reduced sumoylation level was depends on SUMO-interacting motif (SIM). Like SUMO-1,sumoylation sites of SUMO-3 also located in lysine 627 residue. SENP2 influenced the nuclear export of MTF-1. We also find that arsenic increased the transcription activity of K627R since the expression of downstream gene increased with the treatment. This phenomenon was different from that of zinc treatment.

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