Wnt/β-catenin 訊息傳遞路徑已被廣為人知與胚胎發育、細胞生長和腫瘤發展息息相關。而參與在其中的Dishevelled (Dvl)和β-catenin也扮演了很重要的角色。典型的Wnt訊號傳遞路徑是由Wnt配體與跨模受體(Frizzled)及共受體(LRP6)結合，進而使Dvl往膜上聚集且抑制GSK-3β磷酸化β-catenin，使β-catenin穩定與入核。本實驗室先前以酵母菌雙雜合系統(Yeast two-hybrid)確認Dvl2與微小球蛋白(MSP58)有蛋白質交互作用。本研究發現透過報告基因實驗和即時定量聚合酶連鎖反應檢測Wnt/β-catenin下游基因的表達，在過表達微小球蛋白(MSP58)後都有顯著性下降，表示MSP58在Wnt/β-catenin 訊息傳遞路徑中扮演的是抑制者的角色，然而其中的機制卻尚不清楚。透過免疫螢光染色得知MSP58與Dvl2共同位在細胞質和細胞核中。此外，本研究發現MSP58的過表達不會影響Dvl2和β-catenin的蛋白質穩定性與入核。在之後的研究中，將釐清MSP58抑制Wnt/β-catenin訊息傳遞路徑的分子機制，也提供Wnt/β-catenin訊息傳遞路徑如何調節腫瘤發生一個新的面向。

The Wnt/β-catenin signaling pathway controls cell fate during embryonic development and tissue homeostasis as well as participates in the cancer process. Dishevelled (Dvl) and β-catenin proteins play key roles in this pathway. Canonical Wnt signaling pathway is activated by the binding of extracellular Wnt ligand to the Frizzled (Fz) receptor and co-receptor LRP6, leading to membrane recruitment of Dvl protein and inhibition of β-catenin phosphorylation by GSK-3β, thereby β-catenin stabilization and nuclear translocation. Our previous data showed that the 58-kDa microspherule protein (MSP58) interacts with Dvl2 by yeast two-hybrid assay and overexpression of MSP58 can inhibit Wnt/Dvl2-mediated luciferase reporter and target genes expression. These results indicate that MSP58 functions as a repressor in the Wnt/β-catenin signaling pathway. However, the underlying mechanism is still unclear. Immunofluorescence staining revealed that the two proteins are colocalized both in cytoplasm and nucleus. Additionally, we showed that overexpression of MSP58 didn’t influence the protein levels of Dvl2 and β-catenin, as well as their nuclear targeting. In future studies, I will clarify additional mechanisms associated with MSP58-mediated inhibition of Wnt/β-catenin signaling pathway. This study will provide new insights into the novel regulation of Wnt/β-catenin pathway during tumorigenesis.

柯建佑，探討微小球蛋白(MSP58)與SWI/SNF複合體之間交互作用，國立成功大學生物資訊與訊息傳遞研究所碩士論文，2016。

馬郁翔，探討微小球蛋白(MSP58)與Inversin蛋白之間交互作用，國立成功大學生物科技與產業科學系碩士論文，2018。

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