目前於桿狀病毒昆蟲細胞表現系統中已成功表達多種重組蛋白，除了高產量的優勢，也保有蛋白質之重要功能。此優勢使此系統成為應用於生產重組蛋白最為廣用的方法之一。然而相較於細胞質蛋白亦或核蛋白，於細胞中生產分泌性蛋白或是膜蛋白之產量通常較為稀少。在第二及第三章中，我利用分泌性人類鹼性磷酸酶 (SEAP) 與綠螢光蛋白 (eGFP) 所構成之融合蛋白 (SEFP) 做為模型蛋白，以分析SEFP蛋白轉譯或轉錄被調控的程度，鑑定出有潛力可增益分泌性蛋白產量之基因。將欲測試基因與SEFP構築於雙效表現載體上，可於昆蟲細胞中共表現兩個蛋白質。欲測試之基因可分為三類 (i) 轉譯起始因子，eIF4E (ii) 內質網伴護蛋白, calreticulin (CALR)，以及 (iii) 類小熱休克蛋白，α-synuclein (α-syn) 和β-synuclein (β-syn)。利用SEAP酵素活性分析以及西方點墨法比較控制組-類熱休克蛋白40基因與上述基因對於增益 SEFP 分泌產量的情形。再者，SEFP融合蛋白特有的環狀型態加速了在螢光顯微鏡下觀測追蹤重組病毒的表現。更進一步地，利用定量PCR分析每組重組病毒感染細胞後之胞內 mRNA 表現情況。在所有的比較結果中，細胞內若有共表現 α-syn 或 β-syn， SEFP 分泌產量皆有顯著增益，這也許來自轉錄層面的正相調控。而細胞內共表現 eIF4E 時，所增益 SEFP 分泌產量與共表現 CALR 時雖具相當程度，但兩者的作用機制卻不盡相同。最後，利用一個四效表現載體pAcAB4共表現 β-syn，eIF4E，CALR 與SEFP。結果顯示當於細胞中共表現出伴護蛋白與轉譯起始因子時，對SEFP蛋白產量增益效果不僅有加乘作用，也延緩桿狀病毒造成感染後細胞 (Sf9和Sf21) 裂解的時間，此以碘化丙碇染色與西方點墨法證明感染後的細胞膜結構能夠維持在緻密的狀態。在本論文中很清楚的表示，當共表現兩個伴護蛋白及一轉譯起始因子可有效增益分泌性蛋白質的產量，並且延後胞裂的時間。換句話說，此病毒表現載體使感染的細胞有更多的時間進行蛋白質加工，此載體將有利於未來應用於醣蛋白的表現，結構蛋白之研究，以及疫苗開發。

Baculovirus-insect cell expression system (BEVS) is one of the most popular methods used for the production of recombinant proteins owing to its capacity to produce many recombinant proteins at high yield and with functional activities. However, lower yields of secreted or membrane-bound proteins are usually obtained from insect cells than that of cytosol or nucleus proteins. In Chapters 2 and 3 I utilized a SEAP-eGFP (SEFP) fusion protein as a model reporter to identify potential genes that are able to elevate the production of secreted protein, SEFP, either from translational or transcriptional regulation. A series of bicistronic baculovirus vectors were constructed to co-express potential genes with SEFP in insect cells. Among them were (i) translation initiation factor, eIF4E; (ii) ER chaperone, calreticulin (CALR); and (iii) sHSP-like proteins, α-synuclein (α-syn) and β-synuclein (β-syn). SEAP enzymatic analysis and Western blot were carried out for comparison of enhanced extracellular proteins by candidate proteins with that of a negative control, Hsp40-like protein. In addition, expression of SEFP fusion protein in recombinant viruses provides a rapid method to trace the morphology of the special ring shape of SEFP under a fluorescent microscope. The mRNA expression level from each recombinant virus-infected cell was further analyzed by quantitative PCR. In all instances, cells co-expressed with α- and β-synuclein showed a greatly enhanced level of SEFP production and this might come from transcriptional up-regulation. A comparable SEFP production in cells co-expressed eIF4E was obtained when compared with that of the CALR co-expressed cells, although that was governed by a different mechanism. Finally, I co-expressed β-syn, eIF4E and CALR together with SEFP using a quadruple vector, pAcAB4. Not only an additive effect on SEFP production was shown, but also a prolonged life span in the infected Sf9 and 21 cell lines. Propidium iodide staining and Western blot were conducted for demonstrating the compactness of the infected cell membranes. In this thesis, it is clearly showed that the co-expression of chaperones and translation initiation factor facilitate production of secreted protein with a significantly delayed cell lysis. In other words, this quadruple baculovirus vector provides a longer time for protein processing in infected cells and will certainly facilitate glycol-protein production, structural protein research, and vaccine development for future applications.

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