直近一年間の累計
アクセス数 : ?
ダウンロード数 : ?
ID 116405
著者
Ochi, Shintaro Tokushima University
Satoh, Hidetoshi Tokyo University of Science
Ujita, Shohei Tokushima University
Matsushita, Yosuke Tokushima University|Nagasaki University
Tada, Kasumi Tokushima University
Toyoda, Mihiro Tokushima University
Mizuno, Kosuke Tokyo University of Science
Deguchi, Yuichi Nagasaki University
Suzuki, Keiji Nagasaki University
Tanaka, Yoshimasa Nagasaki University
Ueda, Hiroshi Nagasaki University
Inaba, Toshiya Hiroshima University
Hosoi, Yoshio Tohoku University
Aoki, Shin Tokyo University of Science
キーワード
p53
RNA synthesis inhibitor
DNA intercalator
apoptosis
資料タイプ
学術雑誌論文
抄録
RNA synthesis inhibitors and protein synthesis inhibitors are useful for investigating whether biological events with unknown mechanisms require transcription or translation; however, the dependence of RNA synthesis has been difficult to verify because many RNA synthesis inhibitors cause adverse events that trigger a p53 response. In this study, we screened a library containing 9600 core compounds and obtained STK160830 that shows anti-apoptotic effects in irradiated wild-type-p53-bearing human T-cell leukemia MOLT-4 cells and murine thymocytes. In many of the p53-impaired cells and p53-knockdown cells tested, STK160830 did not show a remarkable anti-apoptotic effect, suggesting that the anti-apoptotic activity is p53-dependent. In the expression analysis of p53, p53-target gene products, and reference proteins by immunoblotting, STK160830 down-regulated the expression of many of the proteins examined, and the downregulation correlated strongly with its inhibitory effect on cell death. mRNA expression analyses by qPCR and nascent RNA capture kit revealed that STK160830 showed a decreased mRNA expression, which was similar to that induced by the RNA synthesis inhibitor actinomycin D but differed to some extent. Furthermore, unlike other RNA synthesis inhibitors such as actinomycin D, p53 accumulation by STK160830 alone was negligible, and a DNA melting-curve analysis showed very weak DNA-intercalating activity, indicating that STK160830 is a useful inhibitor for RNA synthesis without triggering p53-mediated damage responses.
掲載誌名
Life
ISSN
20751729
出版者
MDPI
11
10
開始ページ
1087
発行日
2021-10-15
権利情報
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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
出版社版
部局
医学系