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アイテム
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Initially eIF5A was identified to be a translation initiation factor. However recent findings suggested that eIF5A is not involved in translation initiation but has a role in translation elongation and other cellular processes such as mRNA transport. eIF5A is quite unique as it is the only cellular protein containing an unusual, polyamine-derived amino acid, hypusine [Nε- (4-amino 2-hydroxybutyl) lysine]. A conserved lysine residue of eIF5A i.e., lysine 50 of human eIF5A, is modified to hypusine. eIF5A undergoes acetylation, at lysine 47. Our lab previously reported that acetylation regulates subcellular distribution of eIF5A and that acetylated eIF5A localizes to the nucleus. Regulation of eIF5A acetylation by cellular environment is unknown. In the current study I focused to reveal a novel function of eIF5A, under different cellular environments.\nIn order to unravel the role of eIF5A, I studied physiological conditions promoting eIF5A acetylation. I found glucose and hypoxia as the cellular cues of eIF5A acetylation induction. eIF5A was found to be an important factor for cell growth and survival in hypoxia. Furthermore, I found that hypusinated eIF5A is essential for the expression of HIF-1α in hypoxia. In the absence of eIF5A HIF-1α is degraded by the proteasome. My study revealed the importance of eIF5A in tumor growth and survival. On the basis of my observations, it is suggested that hypusination of eIF5A may be a potential target for therapeutic intervention.", "subitem_description_type": "Abstract"}]}, "item_113_description_24": {"attribute_name": "目次", "attribute_value_mlt": [{"subitem_description": "Chapter 1: Introduction\n1.1 Eukaryotic initiation factor 5A (eIF5A)……………………………1\n1.2 Post-translational modifications of eIF5A……………………………1\n1.3 Role of eIF5A in translation…………………………………………2\n1.4 Role of eIF5A in cancer………………………………………………3\nChapter 2: Regulation of eIF5A acetylation\n2.1 Introduction…………………………………………………………………07\n2.2 Materials and methods……………………………………………………09\n2.2.1 Compounds and cell culture\n2.2.2 Antibodies and immunoblotting\n2.2.3 Hypoxic conditions\n2.3 Results and discussion……………………………………………………10\n2.3.1 Increasing glucose concentration induced acetylation of eIF5A\n2.3.2 acetylation of eIF5A is induced by hypoxia\n2.3.3 Effect of HDAC inhibitors and hypoxia on eIF5A acetylation\nSummary…………………………………………………………………………11\nChapter 3: eIF5A is essential for HIF-1α expression in hypoxia\n3.1 Introduction…………………………………………………………………14\n3.1.1 Hypoxia inducible factor 1 alpha (HIF-1α)\n3.1.2 Regulation of HIF-1α\n3.1.3 HIF-1α and cancer progression\n3.2 Materials and methods……………………………………………………18\n3.2.1 Compounds and cell culture\n3.2.2 Antibodies and immunoblotting\n3.2.3 RNAi and hypoxia\n3.2.4 GC7 treatment and hypoxia\n3.3 Results and discussion……………………………………………………19\n3.3.1 Time course of eIF5A acetylation and HIF-1α expression is different\n3.3.2 eIF5A is essential for HIF-1α expression in hypoxia\n3.3.3 Functional eIF5A is important for HIF-1α expression in hypoxia\n3.3.4 GC7 treatment or eIF5A knockdown-mediated suppression of HIF-1α is independent of prolyl hydroxylase (PHD)\n3.3.5 Mechanism of HIF-1α suppression by GC7 treatment or eIF5A knockdown\nSummary……………………………………………………………………22\nChapter 4: eIF5A is required HIF-1α-mediated transcriptional activation in hypoxia\n4.1 Introduction………………………………………………………………29\n4.2 Materials and methods…………………………………………………30\n4.2.1 Compounds and cell culture\n4.2.2 Antibodies and immunoblotting\n4.2.3 RNA interference, GC7 treatment and hypoxia\n4.2.4 RNA extraction and qPCR\n4.3 Results and discussion…………………………………………………32\nSummary……………………………………………………………………33\nChapter 5: eIF5A is important for growth of tumor spheroid\n5.1 Introduction………………………………………………………………37\n5.2 Materials and methods…………………………………………………38\n5.2.1 Compounds and cell culture\n5.2.2 Antibodies and immunoblotting\n5.2.3 RNA interference and GC7 treatment\n5.3 Results and discussion………………………………………………39\n5.3.1 HIF-1α knockdown leads to reduction in the size of spheroid\n5.3.2 eIF5A knockdown has negative effect on spheroid growth\n5.3.3 Functional eIF5A is essential for spheroid growth\nSummary……………………………………………………………………40\nChapter 6: Conclusions…………………………………… 44\nReferences\nReferences…………………………………………………………45", 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A novel role of elF5A in HIF-1α-mediated hypoxic response
https://doi.org/10.24561/00010389
https://doi.org/10.24561/000103893e4c88a9-1492-44df-8cc0-5901dc399cfd
名前 / ファイル | ライセンス | アクション |
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GD0000744.pdf (5.3 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
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公開日 | 2016-12-14 | |||||||||
タイトル | ||||||||||
言語 | en | |||||||||
タイトル | A novel role of elF5A in HIF-1α-mediated hypoxic response | |||||||||
言語 | ||||||||||
言語 | eng | |||||||||
資源タイプ | ||||||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||
資源タイプ | doctoral thesis | |||||||||
ID登録 | ||||||||||
ID登録 | 10.24561/00010389 | |||||||||
ID登録タイプ | JaLC | |||||||||
アクセス権 | ||||||||||
アクセス権 | open access | |||||||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||
タイトル(別言語) | ||||||||||
その他のタイトル | HIF-1αを介した低酸素応答における翻訳制御因子 elF5A の新しい機能に関する研究 | |||||||||
著者 |
TARIQ, MOHAMMAD
× TARIQ, MOHAMMAD
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著者 所属 | ||||||||||
埼玉大学大学院理工学研究科(博士後期課程)理工学専攻 | ||||||||||
著者 所属(別言語) | ||||||||||
Graduate School of Science and Engineering, Saitama University | ||||||||||
書誌 | ||||||||||
収録物名 | 博士論文(埼玉大学大学院理工学研究科(博士後期課程)) | |||||||||
書誌情報 |
発行日 2016 |
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出版者名 | ||||||||||
出版者 | 埼玉大学大学院理工学研究科 | |||||||||
出版者名(別言語) | ||||||||||
出版者 | Graduate School of Science and Engineering, Saitama University | |||||||||
形態 | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | viii, 56 p. | |||||||||
学位授与番号 | ||||||||||
学位授与番号 | 甲第1008号 | |||||||||
学位授与年月日 | ||||||||||
学位授与年月日 | 2016-03-24 | |||||||||
学位名 | ||||||||||
学位名 | 博士(理学) | |||||||||
学位授与機関 | ||||||||||
学位授与機関識別子Scheme | kakenhi | |||||||||
学位授与機関識別子 | 12401 | |||||||||
学位授与機関名 | 埼玉大学 | |||||||||
抄録 | ||||||||||
内容記述タイプ | Abstract | |||||||||
内容記述 | Eukaryotic translation initiation factor 5A (eIF5A) is an important cellular protein and is highly conserved from bacteria to humans. eIF5A is essential for cell growth and survival. Initially eIF5A was identified to be a translation initiation factor. However recent findings suggested that eIF5A is not involved in translation initiation but has a role in translation elongation and other cellular processes such as mRNA transport. eIF5A is quite unique as it is the only cellular protein containing an unusual, polyamine-derived amino acid, hypusine [Nε- (4-amino 2-hydroxybutyl) lysine]. A conserved lysine residue of eIF5A i.e., lysine 50 of human eIF5A, is modified to hypusine. eIF5A undergoes acetylation, at lysine 47. Our lab previously reported that acetylation regulates subcellular distribution of eIF5A and that acetylated eIF5A localizes to the nucleus. Regulation of eIF5A acetylation by cellular environment is unknown. In the current study I focused to reveal a novel function of eIF5A, under different cellular environments. In order to unravel the role of eIF5A, I studied physiological conditions promoting eIF5A acetylation. I found glucose and hypoxia as the cellular cues of eIF5A acetylation induction. eIF5A was found to be an important factor for cell growth and survival in hypoxia. Furthermore, I found that hypusinated eIF5A is essential for the expression of HIF-1α in hypoxia. In the absence of eIF5A HIF-1α is degraded by the proteasome. My study revealed the importance of eIF5A in tumor growth and survival. On the basis of my observations, it is suggested that hypusination of eIF5A may be a potential target for therapeutic intervention. |
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目次 | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | Chapter 1: Introduction 1.1 Eukaryotic initiation factor 5A (eIF5A)……………………………1 1.2 Post-translational modifications of eIF5A……………………………1 1.3 Role of eIF5A in translation…………………………………………2 1.4 Role of eIF5A in cancer………………………………………………3 Chapter 2: Regulation of eIF5A acetylation 2.1 Introduction…………………………………………………………………07 2.2 Materials and methods……………………………………………………09 2.2.1 Compounds and cell culture 2.2.2 Antibodies and immunoblotting 2.2.3 Hypoxic conditions 2.3 Results and discussion……………………………………………………10 2.3.1 Increasing glucose concentration induced acetylation of eIF5A 2.3.2 acetylation of eIF5A is induced by hypoxia 2.3.3 Effect of HDAC inhibitors and hypoxia on eIF5A acetylation Summary…………………………………………………………………………11 Chapter 3: eIF5A is essential for HIF-1α expression in hypoxia 3.1 Introduction…………………………………………………………………14 3.1.1 Hypoxia inducible factor 1 alpha (HIF-1α) 3.1.2 Regulation of HIF-1α 3.1.3 HIF-1α and cancer progression 3.2 Materials and methods……………………………………………………18 3.2.1 Compounds and cell culture 3.2.2 Antibodies and immunoblotting 3.2.3 RNAi and hypoxia 3.2.4 GC7 treatment and hypoxia 3.3 Results and discussion……………………………………………………19 3.3.1 Time course of eIF5A acetylation and HIF-1α expression is different 3.3.2 eIF5A is essential for HIF-1α expression in hypoxia 3.3.3 Functional eIF5A is important for HIF-1α expression in hypoxia 3.3.4 GC7 treatment or eIF5A knockdown-mediated suppression of HIF-1α is independent of prolyl hydroxylase (PHD) 3.3.5 Mechanism of HIF-1α suppression by GC7 treatment or eIF5A knockdown Summary……………………………………………………………………22 Chapter 4: eIF5A is required HIF-1α-mediated transcriptional activation in hypoxia 4.1 Introduction………………………………………………………………29 4.2 Materials and methods…………………………………………………30 4.2.1 Compounds and cell culture 4.2.2 Antibodies and immunoblotting 4.2.3 RNA interference, GC7 treatment and hypoxia 4.2.4 RNA extraction and qPCR 4.3 Results and discussion…………………………………………………32 Summary……………………………………………………………………33 Chapter 5: eIF5A is important for growth of tumor spheroid 5.1 Introduction………………………………………………………………37 5.2 Materials and methods…………………………………………………38 5.2.1 Compounds and cell culture 5.2.2 Antibodies and immunoblotting 5.2.3 RNA interference and GC7 treatment 5.3 Results and discussion………………………………………………39 5.3.1 HIF-1α knockdown leads to reduction in the size of spheroid 5.3.2 eIF5A knockdown has negative effect on spheroid growth 5.3.3 Functional eIF5A is essential for spheroid growth Summary……………………………………………………………………40 Chapter 6: Conclusions…………………………………… 44 References References…………………………………………………………45 |
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注記 | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | 主指導教員 : 吉田稔 | |||||||||
版 | ||||||||||
[出版社版] | ||||||||||
著者版フラグ | ||||||||||
出版タイプ | VoR | |||||||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||
資源タイプ | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | text | |||||||||
フォーマット | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | application/pdf | |||||||||
作成日 | ||||||||||
日付 | 2016-12-14 | |||||||||
日付タイプ | Created | |||||||||
アイテムID | ||||||||||
GD0000744 |