| Item type |
文献 / Documents(1) |
| 公開日 |
2021-10-22 |
| アクセス権 |
|
|
アクセス権 |
open access |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
|
|
|
関連識別子 |
https://doi.org/10.3390/life11101087 |
|
|
関連名称 |
10.3390/life11101087 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
A Novel RNA Synthesis Inhibitor, STK160830, Has Negligible DNA-Intercalating Activity for Triggering A p53 Response, and Can Inhibit p53-Dependent Apoptosis |
| 著者 |
森田, 明典
オチ, シンタロウ
サトウ, ヒデトシ
ウジタ, ショウヘイ
マツシタ, ヨウスケ
タダ, カスミ
トヨダ, ミヒロ
西山, 祐一
ミズノ, コウスケ
デグチ, ユウイチ
スズキ, ケイジ
タナカ, ヨシマサ
ウエダ, ヒロシ
イナバ, トシヤ
ホソイ, ヨシオ
アオキ, シン
|
| 抄録 |
|
|
内容記述 |
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. |
| キーワード |
|
|
主題 |
p53 |
| キーワード |
|
|
主題 |
RNA synthesis inhibitor |
| キーワード |
|
|
主題 |
DNA intercalator |
| キーワード |
|
|
主題 |
apoptosis |
| 書誌情報 |
en : Life
巻 11,
号 10,
p. 1087,
発行日 2021-10-15
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
20751729 |
| 出版者 |
|
|
出版者 |
MDPI |
| 権利情報 |
|
|
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/). |
| EID |
|
|
識別子 |
382829 |
| 言語 |
|
|
言語 |
eng |
life_11_10_1087.pdf (2.97 MB)
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