urora-A 是一個 serine/threonine 的蛋白激脢，會透過磷酸化下游目標蛋白來調
控細胞週期的演進。Aurora-A 被許多研究發現在多種癌症中都有過度表現的情 形，其中包括肝癌。已知 Maf1 是一個 RNA Polymerase III 的 repressor，其活性 取決於磷酸化狀態與其在細胞內的定位。RNA Polymerase III 的產物在癌細胞中 有上調的現象並且也與細胞週期調控有關。實驗室先前的研究發現 Maf1 蛋白在 Aurora-A 過量表現的細胞有增多的跡象，且大部分會被留在細胞質內和增加穩 定性。本研究發現 Aurora-A 會與 Maf1 蛋白 C 端有交互作用，並且也找出 Maf1 潛在受 Aurora-A 磷酸化的位點，同時發現該位點與 Maf1 在細胞內定位與穩定 性有關。有趣的是，本研究發現該位點突變的 Maf1 蛋白雖然絕大部分入核，但 卻失去了抑制 RNA Polymerase III 活性的能力。相對於沒有突變的 Maf1，本研 究發現 Aurora-A 在增加位點突變 Maf1 蛋白的穩定性上能力較差;Aurora-A 夠 與位點突變 Maf1 仍具有交互作用的能力。因此，本研究認為 Aurora-A 可能會 同時以激酶依賴性以及非激脢依賴性的方式調控 Maf1 的細胞內定位與蛋白質 的穩定性。最後，本研究發現細胞質中的 Maf1 會跑到粒線體，而且這會受到 Aurora-A 所調控;因此推斷 Maf1 可能存在著一些細胞核以外的新穎性功能。總 而言之，本研究釐清了一小部分 Aurora-A 與 Maf1 的部分調控機制;然而，對 於 Maf1 在粒線體中的功能，以及 Aurora-A 對於 Maf1 的調控在粒線體中的角 色，則需要更進一步的探討。

Aurora-A plays a vital role in regulating centrosome functions and promoting cell cycle progression. Overexpression of Aurora-A has been observed in a variety of cancers, including hepatocellular carcinoma (HCC). Maf1 is a kind of phosphoprotein which negatively regulates RNA Polymerase III activity. Both phosphorylation and subcellular localization dictate Maf1 activity. The transcripts of RNA polymerase III are upregulated in various cancers which are associated with the cell cycle progression of tumors. Our previous results showed that Aurora-A-overexpressing cells could increase Maf1 total protein level, cytosolic localization, and protein stability. Here, we demonstrated that Aurora-A can form a complex with Maf1 via interacting with its C-domain. A potential Aurora- A phosphorylation site of Maf1 was identified and mutated; we found that this mutant majorly resides in the nucleus but with a loss of function in suppressing RNA Polymerase III activity and promoting cancer cell proliferation. Moreover, this phosphorylation site was found to be crucial for maintaining Maf1 protein stability. Interestingly, compared with the wild-type Maf1, Aurora-A is still able to promote the protein stability of the phosphorylation-deficient Maf1 mutant with less ability. Co- immunoprecipitation assay also found that this mutant retains the interaction ability with Aurora-A. Those results suggested that Aurora-A might regulate Maf1 in both kinase-dependent and kinase- independent manners. Additionally, our recent discovery indicated that Maf1 also localizes in mitochondria fraction which could be enhanced by Aurora-A overexpression, thereby providing insight that cytosolic Maf1 could regulate mitochondria function in cancer progression. Taken altogether, we provided a connection between Aurora-A and Maf1 in regulating cancer cell progression.

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