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Genome-Scale CRISPR/Cas9 Screening Reveals Squalene Epoxidase as a Susceptibility Factor for Cytotoxicity of Malformin A1
http://hdl.handle.net/10295/00006178
http://hdl.handle.net/10295/000061789b2a10ea-56d6-4aaf-82da-e9397b91dd21
名前 / ファイル | ライセンス | アクション |
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iA_2022_43.pdf (999.1 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2023-02-19 | |||||
タイトル | ||||||
タイトル | Genome-Scale CRISPR/Cas9 Screening Reveals Squalene Epoxidase as a Susceptibility Factor for Cytotoxicity of Malformin A1 | |||||
言語 | en | |||||
言語 | ||||||
言語 | eng | |||||
主題 | ||||||
主題Scheme | Other | |||||
主題 | CRISPR | |||||
主題 | ||||||
主題Scheme | Other | |||||
主題 | Cas9 | |||||
主題 | ||||||
主題Scheme | Other | |||||
主題 | cytotoxicity | |||||
主題 | ||||||
主題Scheme | Other | |||||
主題 | malformin | |||||
主題 | ||||||
主題Scheme | Other | |||||
主題 | peptides | |||||
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主題Scheme | Other | |||||
主題 | squalene epoxidase | |||||
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 | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
作成者 |
Koizumi, Yukio
× Koizumi, Yukio× Fukushima, Jun× Kobayashi, Yayoi× Kadowaki, Ayumi× Natsui, Miyuki× Yamaguchi, Tomokazu× Imai, Yumiko× Sugiyama, Toshihiro× Kuba, Keiji |
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内容記述 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Malformin A1 (MA1) is a fungus-produced cyclic pentapeptide. MA1 exhibits teratogenicity to plants, fibrinolysis-enhancing activity, and cytotoxicity to mammalian cells. To clarify the cytotoxic mechanism of MA1, we screened for the genes involved in the cytotoxicity of MA1 in monocytoid U937 cells by using a CRISPR/Cas9-based genome-wide knockout library. Screening was performed by positive selection for cells that were resistant to MA1 treatment, and single guide RNAs (sgRNAs) integrated into MA1-resistant cells were analyzed by high-throughput sequencing. As a result of the evaluation of sgRNAs that were enriched in MA1-resistant cells, SQLE, which encodes squalene epoxidase, was identified as a candidate gene. SQLE-depleted U937 cells were viable in the presence of MA1, and squalene epoxidase inhibitor conferred MA1 resistance to wild-type cells. These results indicate that squalene epoxidase is implicated in the cytotoxicity of MA1. This finding represents a new insight into applications of MA1 for treating ischemic diseases. | |||||
言語 | en | |||||
出版タイプ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
書誌情報 |
en : ChemBioChem 巻 20, 号 12, p. 1563-1568, 発行日 2019 |
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収録物識別子 | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1439-4227 | |||||
出版者 | ||||||
出版者 | John Wiley and Sons Inc | |||||
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関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1002/cbic.201800769 | |||||
権利情報 | ||||||
権利情報 | © 2019The Authors.Publishedby Wiley-VCHVerlagGmbH&Co. KGaA.This is an openaccess article underthe termsof the Creative Commons At-tributionNon-Commercial NoDerivs License, whichpermitsuse and distri-butionin any medium, provided the original workis properly cited,the useis non-commercial and no modificationsor adaptationsare made. |