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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 胡孟君(Meng-Chun Hu) | |
| dc.contributor.author | Yu-Chen Tai | en |
| dc.contributor.author | 戴予辰 | zh_TW |
| dc.date.accessioned | 2021-06-14T16:42:57Z | - |
| dc.date.available | 2010-09-11 | |
| dc.date.copyright | 2008-09-11 | |
| dc.date.issued | 2008 | |
| dc.date.submitted | 2008-07-30 | |
| dc.identifier.citation | Aravind L, Koonin EV. 2000. SAP - a putative DNA-binding motif involved in chromosomal organization. Trends Biochem Sci 25:112-114.
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Mol Endocrinol 18:1988-1999. 潘建廷. 2005. LRH-1抗體製備及LRH-1調控CYP11A1之研究. 生理學研究所. 台灣大學. 吳美伶. 2006. LRH-1轉錄活性調控之研究. 生理學研究所. 台灣大學. 謝祥燦. 2007. LRH-1特性及其轉錄活性受PIASy調控之探討. 生理學研究所. 台灣大學. 王志宏. 2008. mLRH-1 結構功能之探討：PIASy 作用區、Hinge 結構區及核定位訊號. 生理學研究所. 台灣大學. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/40226 | - |
| dc.description.abstract | PIASy是PIAS蛋白家族中的一員，參與許多訊息傳導路徑的調控。其調控的機制大多為調控轉錄因子的活性，包含干擾轉錄因子與DNA的結合，或是招募一些輔因子。此外，PIASy具有SUMO E3 ligase活性，因此也可以透過Sumoylation調節轉錄因子活性。H295為人類腎上腺腫瘤細胞，可以表現腎上腺皮質中許多固醇類荷爾蒙生成酵素，也可以分泌許多固醇類荷爾蒙。我們發現，在H295細胞當中，PIASy會調控固醇類生成酵素基因的表現。PIASy會抑制CYP11A1及StAR啟動子的表現，而且這個現象具有劑量依存性。CYP11A1的蛋白質產物為P450scc，是催化固醇類荷爾蒙生成第一個步驟的酵素。我們將PIASy蛋白過量表現在H295中，發現其內生性P450scc的蛋白表現量下降，顯示PIASy會抑制H295內生性的CYP11A1基因表現。在H295細胞中，可以偵測到PIASy蛋白的表現，所以我們進一步使用RNAi，降低內生性PIASy的表現，結果顯示P450scc的表現有上升的趨勢，也再度證明的我們的假設。
當我們刪除PIASy蛋白的兩個抑制區 (Repression Domain) 中的第一抑制區 (RD1)，抑制CYP11A1啟動子的現象即消失，顯示RD1是負責PIASy對於CYP11A1啟動子的抑制作用。此外，我們發現PIASy的抑制作用與SF-1、LRH-1及AP1/CREB like protein等調控CYP11A1基因的轉錄因子無關。於是我們利用不同長度的CYP11A1啟動子，發現PIASy抑制作用的區域，可能在CYP11A1上游0.5 kb的啟動子之內。我們的結論是，PIASy可以抑制CYP11A1基因的表現，因此可能參與腎上腺皮質等內分泌器官中固醇類荷爾蒙生成的調控。 | zh_TW |
| dc.description.abstract | PIASy, a member of protein inhibitor of activated STAT (PIAS) family, is a coregulator involved in many signal pathways. PIASy modulates the transcriptional activity of various proteins though multiple mechanism, such as interfering the binding with DNA or recruiting cofactors. Also as a SUMO E3 ligase, PIASy can affect the trans-activity of transcriptional factors through sumoylation. H295 is a human adrenocortical carcinoma cell line which can express various steroidogenic enzymes and secrete steroid hormones. In the present study, we found out that PIASy regulates steroidogenic gene in H295. PIASy repressed the promoter activity of CYP11A1 and StAR in a dose-dependant manner. P450scc is encoded by CYP11A1 and catalyses the first step of steroidogenesis. Overexpression of PIASy in H295 cells leaded to decreased amount of endogenous P450scc. Moreover, we used RNAi to knock down endogenous PIASy in H295 and found that P450scc was slightly up-regulated. These results suggest that PIASy represses the endogenous CYP11A1 gene expression.
The repression ability vanished when one of the repression domain, repression domain 1 (RD1), was deleted from PIASy. Thus we conclude that RD1 is responsible for the PIASy-mediated repression effect on CYP11A1 promoter. The repression effect of PIASy is not related to the transcriptional factors including SF-1, LRH-1 or AP1/CREB protein. The deletion analysis reveals that the region of PIASy-mediated repression is lacated at 0.5-kb 5’-flanking sequence of CYP11A1 promoter. Taken together, PIASy represses the expression of CYP11A1 gene in H295 and may participate in regulating steroidogenesis in endocrine organs like adrenal gland. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-14T16:42:57Z (GMT). No. of bitstreams: 1 ntu-97-R95441002-1.pdf: 526385 bytes, checksum: a9168810efeea00db53c88ad0ca329ac (MD5) Previous issue date: 2008 | en |
| dc.description.tableofcontents | 致謝----------------------------------------------I
目錄----------------------------------------------II 圖次----------------------------------------------IV 中文摘要------------------------------------------V 英文摘要------------------------------------------VI 第一章 序論---------------------------------------1 一、PIASy簡介-------------------------------------1 (一) PIASy的構造----------------------------------1 (二) PIASy的功能----------------------------------2 二、腎上腺皮質中固醇類荷爾蒙的生成與調控----------3 (一)腎上腺皮質的構造------------------------------3 (二)固醇類荷爾蒙的生成----------------------------3 (三)固醇類荷爾蒙的調控----------------------------4 (四)CYP11A1基因的調控機制-------------------------5 三、人類腎上腺皮質腫瘤細胞株 (H295)簡介-----------7 四、研究動機--------------------------------------7 第二章 材料與方法---------------------------------9 一、細胞培養--------------------------------------9 二、質體建構--------------------------------------9 三、暫時轉染法 (Transient transfection)-----------11 四、Luciferase活性分析----------------------------12 五、西方墨點法------------------------------------13 第三章 結果---------------------------------------15 一、PIASy表現於小鼠腎上腺及人類腎上腺皮質腫瘤細胞 株(H295)中------------------------------------15 二、H295細胞中PIASy過量表現抑制CYP11A1及StAR啟動子 的活性----------------------------------------15 三、PIASy過量表現降低內生性P450scc蛋白在H295細胞中 的表現----------------------------------------16 四、弱化PIASy對P450scc蛋白在H295細胞中表現的效應--16 五、PIASy抑制CYP11A1表現需要RD1區域---------------16 六、PIASy抑制CYP11A1啟動子表現與轉錄因子SF-1的關係17 七、PIASy的抑制作用與活化因子 (activator) 的關係--17 八、PIASy在CYP11A1啟動子的作用區域----------------18 第四章 討論---------------------------------------19 一、內生性PIASy表現在腎上腺中---------------------19 二、PIASy抑制固醇類荷爾蒙生成基因表現-------------19 三、PIASy的RD1區域對其抑制功能是重要的------------20 四、PIASy與轉錄因子的關係-------------------------21 五、其他可能參與的分子----------------------------22 參考文獻------------------------------------------23 圖------------------------------------------------29 | |
| dc.language.iso | zh-TW | |
| dc.subject | 固醇類荷爾蒙生成 | zh_TW |
| dc.subject | 腎上腺細胞 | zh_TW |
| dc.subject | H295 | en |
| dc.subject | PIASy | en |
| dc.subject | Steroidogenic | en |
| dc.title | PIASy抑制人類腎上腺細胞類固醇荷爾蒙生成基因的表現 | zh_TW |
| dc.title | PIASy Represses Steroidogenic Gene Expression in Human adrenocortical Carcinoma Cell H295 | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 96-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 黃娟娟(Jiuan-Jiuan Hwang),張淑芬(Shwu-Fen Chang),楊性芳(Hsin-Fang Yang-Yen),鍾邦柱(Bon-chu Chung) | |
| dc.subject.keyword | 腎上腺細胞,固醇類荷爾蒙生成, | zh_TW |
| dc.subject.keyword | PIASy,H295,Steroidogenic, | en |
| dc.relation.page | 28 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2008-08-01 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生理學研究所 | zh_TW |
| 顯示於系所單位： | 生理學科所 | |
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