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ID 110161
著者
Kajita, K Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School
桑野, 由紀 Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School 徳島大学 教育研究者総覧 KAKEN研究者をさがす
Satake, Y Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School
Kano, S Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School
Kurokawa, K Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School
Akaike, Y Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School
増田, 清士 Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School KAKEN研究者をさがす
西田, 憲生 Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School 徳島大学 教育研究者総覧 KAKEN研究者をさがす
六反, 一仁 Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School 徳島大学 教育研究者総覧 KAKEN研究者をさがす
資料タイプ
学術雑誌論文
抄録
Ultraconserved regions (UCRs) are 4200 bp genomic segments with perfect human-to-rodent sequence identity. Transcribed UCRs constitute a new category of noncoding RNAs whose functions remain poorly understood. The human transformer 2β (TRA2B) gene contains a 419-bp UCR spanning the 276-bp exon 2 and its neighboring introns. TRA2B exon 2 has premature stop codons, whereas an exon 2-containing splice variant (TRA2β4) was expressed preferentially in the nuclei of human colon cancer cells. TRA2β4 knockdown p53-independently stimulated CDKN1A transcription and increased p21, resulting in the appearance of senescent cells. Biotin pull-down and RNA immunoprecipitation assays revealed that TRA2β4 interacted with Sp1 through a Sp1-binding sequence (485-GGGG-488) in a stem-loop structure of exon 2. Mutation of this sequence (485-AAGG-488) disrupted the stem-loop structure, blocked the interaction with Sp1 and increased CDKN1A transcription. Overexpression of TRA2β4 significantly decreased CDKN1A mRNA levels and accelerated cell growth, but the introduction of the mutation in the Sp1-binding sequence completely canceled these effects. Taken together, TRA2β4 may sequester Sp1 from occupying promoters of target genes including CDKN1A, promoting cell growth by interrupting the senescence-related gene expression program. This novel function of TRA2β4 may uncover an oncogenic function of transcribed UCRs.
掲載誌名
Oncogenesis
ISSN
21579024
5
開始ページ
e213
並び順
213
発行日
2016-04-04
備考
Oncogenesis is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系