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ID 109685
タイトル別表記
酸化ストレスにより誘導されるtruncated serine/arginine –rich splicing factor 3はヒト大腸癌細胞のインターロイキン8の産生を調節する
Truncated SRSF3 regulates IL-8 production
著者
狩野, 静香 徳島大学大学院医科学教育部(医学専攻)
Kurebe, Hiroyuki The University of Tokushima
Nishiyama, Chihiro The University of Tokushima
Kita, Kentaro The University of Tokushima
Akaike, Yoko The University of Tokushima
Kajita, Keisuke The University of Tokushima
Kurokawa, Ken The University of Tokushima
増田, 清士 The University of Tokushima KAKEN研究者をさがす
棚橋, 俊仁 The University of Tokushima
キーワード
SRSF3遺伝子
酸化ストレス
選択的スプライシング
ナンセンス変異依存mRNA分解機構
インターロイキン8
SRSF3 gene
oxidative stress
alternative splicing
nonsense-mediated mRNA decay
IL-8
資料タイプ
学位論文
抄録
Serine/arginine-rich splicing factor 3 (SRSF3) is a member of the SR protein family and plays wide-ranging roles in gene expression. The human SRSF3 gene generates two alternative splice transcripts, a major mRNA isoform (SRSF3-FL) encoding functional full-length protein and a premature termination codon (PTC)-containing isoform (SRSF3-PTC). The latter is degraded through nonsense-mediated mRNA decay (NMD). Treatment of a human colon cancer cell line (HCT116) with 100 μM sodium arsenite increased SRSF3-PTC mRNA levels without changing SRSF3-FL mRNA levels. A chemiluminescence-based NMD reporter assay system demonstrated that arsenite treatment inhibited NMD activity and increased SRSF3-PTC mRNA levels in the cytoplasm, facilitating translation of a truncated SRSF3 protein (SRSF3-TR) from SRSF3-PTC mRNA. SRSF3-TR lacked two-thirds of Arg/Ser-rich (RS) domain whose phosphorylation state is known to be crucial for subcellular distribution. SRSF3-FL was localized in the nucleus, while overexpressed SRSF3-TR was diffusely distributed in the cytoplasm and the nucleus. A part of SRSF3-TR was also associated with stress granules in the cytoplasm. Interestingly, treatment of HCT116 cells with a small interference RNA specifically targeting SRSF3-PTC mRNA significantly attenuated arsenite-stimulated induction of c-JUN protein, its binding activity to the AP-1 binding site (-126 to 120 bp) in the interleukin (IL)-8 gene promoter, and AP-1 promoter activity, resulting in significant reduction of arsenite-stimulated IL-8 production. Our results suggest that SRSF3-TR may function as a positive regulator of oxidative stress-initiated inflammatory responses in colon cancer cells.
掲載誌名
American Journal of Physiology. Cell Physiology
ISSN
03636143
15221563
cat書誌ID
AA00521122
出版者
the American Physiological Society
306
3
開始ページ
C250
終了ページ
C262
発行日
2014-02-01
備考
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨 : LID201606061012.pdf
論文本文 : k2903_fulltext.pdf
本論文は,著者Shizuka Kano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。
著者の申請により要約(2016-06-07公開)に替えて論文全文を公開(2019-12-19)
権利情報
© 2014 the American Physiological Society
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2903号
学位記番号
甲医第1277号
学位授与年月日
2016-03-23
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系