| ID | 109685 |
| Title Alternative | 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
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| Author |
Kano, Shizuka
The University of Tokushima
Nishida, Kensei
The University of Tokushima
Tokushima University Educator and Researcher Directory
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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
Kuwano, Yuki
The University of Tokushima
Tokushima University Educator and Researcher Directory
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Tanahashi, Toshihito
The University of Tokushima
Rokutan, Kazuhito
The University of Tokushima
Tokushima University Educator and Researcher Directory
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| Keywords | 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
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| Content Type |
Thesis or Dissertation
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| Description | 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.
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| Journal Title |
American Journal of Physiology. Cell Physiology
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| ISSN | 03636143
15221563
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| NCID | AA00521122
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| Publisher | the American Physiological Society
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| Volume | 306
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| Issue | 3
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| Start Page | C250
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| End Page | C262
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| Published Date | 2014-02-01
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| Remark | 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) |
| Rights | © 2014 the American Physiological Society
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| EDB ID | |
| DOI (Published Version) | |
| URL ( Publisher's Version ) | |
| FullText File | |
| language |
eng
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| TextVersion |
ETD
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| MEXT report number | 甲第2903号
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| Diploma Number | 甲医第1277号
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| Granted Date | 2016-03-23
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| Degree Name |
Doctor of Medical Science
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| Grantor |
Tokushima University
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| departments |
Medical Sciences
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