58-kDa微小球蛋白(MSP58) 是一種核仁蛋白，其在生物演化上非常保守，且對於細胞維持的功能上扮演重要的角色，包括細胞轉型、細胞增生以及轉錄調控等。而到目前為止，對於MSP58在致癌基因的定位仍需要進一步的研究釐清。我們使用酵母菌雙雜合分析法(Yeast Two-hybrid Screening) 想去找尋並探討MSP58與其結合蛋白之間的交互作用。而在這一系列蛋白之中，我們目前主要專注在Inversin這個蛋白。Inversin又被稱作是Nephrocystin-2(NPHP)蛋白，屬於Nephrocystin蛋白家族中的一員，同時也是第二型腎囊腫(NPHP2) 中的纖毛蛋白(腎囊腫，是一種體染色體隱性腎臟病)。先前的研究指出，Inversin蛋白在胚胎的發育以及腎臟的疾病中扮演相當重要的角色，但是其在腫瘤形成中的功能尚未被清楚的探討；但近期報導指出Inversin蛋白可以促進肺癌的侵入能力並與非小型細胞肺癌的惡性表型相關。另外，Inversin蛋白也與anaphase-promoting complex 2(APC2)、Aurora A和Akt有交互作用，顯示其可能參與在細胞週期調控。我們希望進一步了解58-kDa微小球蛋白(MSP58)與Inversin蛋白參與在細胞生長和增值的調控的分子機制與其生物意義。這些研究會為我們對於58-kDa微小球蛋白(MSP58)在腫瘤發展的過程中提供一個新的視野來探討其分子機制與功能。

58-kDa microspherule protein (MSP58) is an evolutionarily conserved nuclear/ nucleolar protein and plays a critical role in numerous cellular processes including transcriptional regulation, microtubule organization, cell transformation and senescence. However, the mechanisms underlying the oncogenic activities of MSP58 are not revealed clearly so far. We have used a yeast two-hybrid approach to identify several novel proteins that interact with MSP58. Among them, we are currently focusing on characterizing the Inversin protein. Inversin, also known as Nephrocystin-2, is a ciliary protein encoded by NPHP2 (nephronophthisis). Although previous research has indicated that inversin played an important role in renal diseases and embryonic development, its function in tumorigenesis was not illustrated. A recent study shows that Inversin promotes the invasiveness of lung cancer and correlates with the malignant phenotype and invasiveness of non-small cell lung cancer; the mechanism was unclear. Moreover, Inversin has been reported to interact with anaphase-promoting complex 2 (APC2), Aurora A and Akt, suggesting that it is involved in the regulation of cell cycle progression. We will clarify the biological role of MSP58/Inversin interactions involved in the control of cell proliferation and the cell division. These studies will provide new insights into the molecular mechanisms of MSP58-mediated tumorigenesis.

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