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ID 112030
タイトル別表記
ヌクレオリンは、超保存領域を含むTRA2β4を核内に保持し、大腸がん細胞の増殖を促進する
著者
佐竹, 譲 徳島大学大学院医科学教育部(プロテオミクス医科学専攻)
西川, 達哉 Tokushima University
Fujita, Kinuyo Tokushima University
Saijo, Saki Tokushima University
Itai, Miki Tokushima University
Tanaka, Hiroki Tokushima University
キーワード
nucleolin
transcribed-UCR
TRA2β4
colon cancer
cell growth
資料タイプ
学位論文
抄録
Transcribed-ultraconserved regions (T-UCRs), which contain conserved sequences with 100% identity across human, rat and mouse species, are a novel category of functional RNAs. The human transformer 2β gene (TRA2B) encodes a UCR that spans exon 2 (276 bp) and its neighboring introns. Among five spliced RNA variants (TRA2β1-5) transcribed from the TRA2B gene, only TRA2β4 contains the conserved exon 2. TRA2β4 is overexpressed in colon cancer cells and accelerates cell growth by blocking the transcription of CDKN1A. However, the mechanisms underlying the overexpression of TRA2β4 in colon cancer cells are unknown. Using biotinylated RNA pull-down assays followed by liquid chromatography-mass spectrometric analysis, we identified nucleolin as a TRA2β4-binding protein. Knockdown of nucleolin reduced the nuclear retention of TRA2β4 and accelerated its degradation in the cytoplasm, whereas nucleolin overexpression increased TRA2β4 levels and its mitogenic activity. Nucleolin directly bound to TRA2β4 exon 2 via the glycine/arginine-rich (GAR) domain. Overexpression of GAR-deficient nucleolin failed to increase TRA2β4 expression and growth of colon cancer cells. RNA fluorescence in situ hybridization showed that TRA2β4 co-localized with nucleolin in nuclei but not with the mutant lacking GAR. Our results suggest that specific interactions between nucleolin and UCR-containing TRA2β4 may be associated with abnormal growth of colon cancer cells.
掲載誌名
Oncotarget
ISSN
19492553
出版者
Impact Journals
9
42
開始ページ
26817
終了ページ
26833
発行日
2018-06-01
備考
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Yuzuru Satakeの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
Copyright: Satake et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ( https://creativecommons.org/licenses/by/3.0/ )
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3201号
学位記番号
甲医第1376号
学位授与年月日
2018-07-26
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系