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系統識別號 U0026-0812200914225573
論文名稱(中文) 分析CEBPD 與Rb 在HMDB引發之細胞凋亡相關基因活化的角色扮演
論文名稱(英文) Characterize the functional role of CEBPD/Rb in HMDB-induced apoptotic gene transcription
校院名稱 成功大學
系所名稱(中) 藥理學研究所
系所名稱(英) Department of Pharmacology
學年度 96
學期 2
出版年 97
研究生(中文) 陳姵蓉
研究生(英文) Pei-Jung Pei
學號 S2695402
學位類別 碩士
語文別 中文
論文頁數 66頁
口試委員 口試委員-曾大千
指導教授-張文昌
指導教授-王育民
中文關鍵字 細胞凋亡  抑癌基因  甘草萃取物  生長停滯 
英文關鍵字 PPARG2  HMDB  Rb  CEBPD  GADD153 
學科別分類
中文摘要 CEBPD 為 CCAAT/Enhancer binding protein (C/EBP) 家族成員之
一。已知 CEBPD 在細胞分化,發炎機制及脂質生合成有重要的功能扮演。近年來的一些文獻報導以及實驗室先前的研究顯示 CEBPD 可以誘發細胞的生長停滯並且促進細胞的分化,並且在調控 pro-apoptotic 基因的表現上扮演重要的角色, 是為相當有潛力抑癌基因。已知retinoblastoma protein (Rb) 在細胞週期中扮演一重要角色,目前對於其與E2F1 作用在 G1/S 轉換點的研究最為人熟知。在本論文中,我們發現甘草萃取物其衍生物hydroxydibenzoylmethane (HMDB) 能夠促進CEBPD 在細胞中的轉錄活化作用,同時也活化 PPARG2 和 GADD153基因的表現。此外,我們也證實了 CEBPD 在活體中能與 Rb 有交互作用的關係,並且 Rb 對於 CEBPD 所活化的基因轉錄作用有一負向的調控機制。再者,大量產生的 CEBPD 可對 Rb/E2F1 複合體產生拮抗作用,轉而活化 Rb/E2F1 複合體所抑制的下游基因。
英文摘要 The CCAAT/enhancer-binding protein (CEBP) family of transcription factors plays an important role in controlling cell proliferation and differentiation. CEPBD, one of the CEBP family members, has been reported
to be a potential tumor suppressor because it can induce growth arrest to involve in differentiation and play as a crucial regulator of pro-apoptotic gene expression. Retinoblastoma protein(Rb)is well known to be an important regulator in the G1/S transition or differentiation through the interaction with E2F1. In this study, we found that a DBM structure-related compound -
hydroxymethyldibenzoylmethane (HMDB) can induce CEBPD, PPARG2 and GADD153 transcription. We also demonstrated that Rb physically interacts with CEBPD and plays a negative role in the CEBPD-mediated PPARG2 and
GADD153 transcription. Furthermore, our data suggest that CEBPD can activate the apoptotic gene through the de-repression of Rb/E2F1-mediated gene inactivation.
論文目次 中文摘要……………………………………………………………… I
英文摘要……………………………………………………………… II
致謝…………………………………………………………………… III
圖目錄………………………………………………………………… V
第一章 緒論
前 言…………………………………………………………. 1
第一節 甘草萃取物及其衍生物介紹………………………... 2
第二節 DBM 以及其衍生物 HDB、HMDB 的抑癌作用… 3
第三節 CEBPD 之生理功能………………………………… 3
第四節 GADD153 的功能及特性............................................ 5
第五節 Rb 家族蛋白…............................................................. 7
第六節 E2F 轉錄因子家族....................................................... 8
第七節 PPARG2 之生理功能................................................... 8
第八節 研究動機……………………………………………... 9
第二章 實驗材料及方法
來 源…………………………………………………………. 11
實驗方法………………………………………………………. 16
第三章 實驗結果
第一節 在 A431 中,HMDB 的處理可以活化CEBPD 以
及細胞凋亡相關基因的表現………………………... 33
V
第二節 CEBPD 是 Rb 的互動蛋白………………………… 34
第三節 Rb 具有負向調控 CEBPD 活化下游基因的能力… 35
第四節 CEBPD 可參與在 Rb/E2F1 複合體對於轉錄活化
區的抑制作用的調控................................................... 36
第四章 討論 39
第五章 參考文獻 43
附圖
Figure 01. Structure of the DBM, HDB, HMDB, and curcumin......... 54
Figure 02. The structure of CEBP family............................................ 55
Figure 03. The mammalian pocket protein families and E2F protein
families………………………………………………….. 56
Figure 04. Up-regulation of CEBPD mRNA and protein expression
upon HMDB treatment………………………………….. 57
Figure 05. Up-regulation of apoptosis-related gene transcription
upon HMDB treatment...................................................... 58
Figure 06. Rb physically co-localizes with CEBPD............................ 59
Figure 07. CEBPD interacts with Rb in vivo and in vitro…………... 60
Figure 08. Rb negatively regulates CEBPD-activated genes
expression……………………………………………….. 61
Figure 09. Overexpression of Rb reverses the Rb-inhibitory effect in
Rb-negative cell line.......................................................... 62
Figure 10. CEBPD can be a sequester to reverse Rb/E2F1 repressive
effect in transcription…………………………………... 63
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