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ATRA inhibits ceramide kinase transcription through an ATRA-related transcription factor, COUP-TFI, in a human neuroblastoma cell line, SH-SY5Y
http://hdl.handle.net/2237/14433
http://hdl.handle.net/2237/14433d14831e1-0631-4858-bf66-b96a2d332339
名前 / ファイル | ライセンス | アクション |
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k8661.pdf (810.3 kB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2011-01-07 | |||||
タイトル | ||||||
タイトル | ATRA inhibits ceramide kinase transcription through an ATRA-related transcription factor, COUP-TFI, in a human neuroblastoma cell line, SH-SY5Y | |||||
言語 | en | |||||
その他のタイトル | ||||||
その他のタイトル | ヒト神経芽細胞腫細胞株SH-SY5Y細胞のATRA誘導性転写因子COUP-TFIによるセラミドキナーゼ遺伝子の発現抑制 | |||||
言語 | ja | |||||
著者 |
村上, 真史
× 村上, 真史× MURAKAMI, Masashi |
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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 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | All-trans retinoic acid | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | neuronal differentiation | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | SH-SY5Y cell | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | ceramide kinase | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | promoter analysis | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | COUP-TFI | |||||
抄録 | ||||||
内容記述 | Ceramide is the central lipid in the sphingolipid metabolism. Ceramide kinase (CERK) and its product, ceramide 1-phosphate (C1P), have been implicated in various cellular functions. However, the regulatory mechanism of CERK gene expression remains to be determined. Here, we examined CERK mRNA level during all-trans retinoic acid (ATRA)-induced differentiation of a human neuroblastoma cell line, SH-SY5Y. ATRA reduced CERK mRNA and protein levels. Overexpression and siRNA of CERK revealed that CERK is inhibitory against ATRA-induced neuronal differentiation and cell growth arrest. ATRA inhibited the transcriptional activity of 5’-promoter of CERK. Truncation and mutation study suggests that ATRA-responsible region was mainly located in the tandem retinoic acid responsive elements (RARE) between -40 bp and the first exon. The electrophoresis mobility shift assay revealed that ATRA produced two retarded bands, which were erased by antibody against COUP-TFI, RARα and RXRα, respectively. DNA pull-down assay confirmed increased binding of these transcription factors to RARE. Transient expression of RAR, RXR and COUP-TFI and siRNA transfection of these genes revealed that COUP-TFI inhibited CERK mRNA. Furthermore, chromatin immunoprecipitation assay showed the recruitment of co-repressors as well as three transcription factors. These results suggest that COUP-TFI was the ATRA-responsive suppressive transcription factor of CERK gene transcription. | |||||
言語 | en | |||||
内容記述タイプ | Abstract | |||||
内容記述 | ||||||
内容記述 | 名古屋大学博士学位論文 学位の種類:博士(医療技術学) (課程) 学位授与年月日 平成22年3月25日 | |||||
言語 | ja | |||||
内容記述タイプ | Other | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_db06 | |||||
タイプ | doctoral thesis | |||||
書誌情報 |
発行日 2010-03-25 |
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学位名 | ||||||
言語 | ja | |||||
学位名 | 博士(医療技術学) | |||||
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 | 13901 | |||||
言語 | ja | |||||
学位授与機関名 | 名古屋大学 | |||||
言語 | en | |||||
学位授与機関名 | NAGOYA University | |||||
学位授与年度 | ||||||
学位授与年度 | 2009 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2010-03-25 | |||||
学位授与番号 | ||||||
学位授与番号 | 甲第8661号 | |||||
著者版フラグ | ||||||
値 | publisher | |||||
URI | ||||||
識別子 | http://hdl.handle.net/2237/14433 | |||||
識別子タイプ | HDL |