| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-03-31 |
| タイトル |
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タイトル |
Inhibition of PRMT5/MEP50 Arginine Methyltransferase Activity Causes Cancer Vulnerability in NDRG2low Adult T-Cell Leukemia/Lymphoma |
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言語 |
en |
| 言語 |
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言語 |
eng |
| キーワード |
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言語 |
en |
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キーワード |
ATL |
| キーワード |
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言語 |
en |
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キーワード |
MEP50 |
| キーワード |
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言語 |
en |
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キーワード |
NDRG2 |
| キーワード |
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言語 |
en |
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キーワード |
PRMT5 |
| キーワード |
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言語 |
en |
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キーワード |
cancer vulnerability |
| 資源タイプ |
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資源タイプ |
journal article |
| アクセス権 |
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アクセス権 |
open access |
| 著者 |
Ichikawa, Tomonaga
Suekane, Akira
Nakahata, Shingo
Iha, Hidekatsu
下田, 和哉
WEKO
7997
e-Rad_Researcher
90311844
| en |
Shimoda, Kazuya
University of Miyazaki
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| ja |
下田, 和哉
宮崎大学
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| ja-Kana |
シモダ, カズヤ
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Search repository
Murakami, Takashi
森下, 和広
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
N-myc downstream-regulated gene 2 (NDRG2), which is a tumour suppressor, is frequently lost in many types of tumours, including adult T-cell leukaemia/lymphoma (ATL). The downregulation of NDRG2 expression is involved in tumour progression through the aberrant phosphorylation of several important signalling molecules. We observed that the downregulation of NDRG2 induced the translocation of protein arginine methyltransferase 5 (PRMT5) from the nucleus to the cytoplasm via the increased phosphorylation of PRMT5 at Serine 335. In NDRG2low ATL, cytoplasmic PRMT5 enhanced HSP90A chaperone activity via arginine methylation, leading to tumour progression and the maintenance of oncogenic client proteins. Therefore, we examined whether the inhibition of PRMT5 activity is a drug target in NDRG2low tumours. The knockdown of PRMT5 and binding partner methylsome protein 50 (MEP50) expression significantly demonstrated the suppression of cell proliferation via the degradation of AKT and NEMO in NDRG2low ATL cells, whereas NDRG2-expressing cells did not impair the stability of client proteins. We suggest that the relationship between PRMT5/MEP50 and the downregulation of NDRG2 may exhibit a novel vulnerability and a therapeutic target. Treatment with the PRMT5-specific inhibitors CMP5 and HLCL61 was more sensitive in NDRG2low cancer cells than in NDRG2-expressing cells via the inhibition of HSP90 arginine methylation, along with the degradation of client proteins. Thus, interference with PRMT5 activity has become a feasible and effective strategy for promoting cancer vulnerability in NDRG2low ATL. |
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言語 |
en |
| 内容記述 |
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内容記述タイプ |
Other |
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内容記述 |
Citation: Ichikawa, T.; Suekane, A.; Nakahata, S.; Iha, H.; Shimoda, K.; Murakami, T.; Morishita, K. Inhibition of PRMT5/MEP50 Arginine Methyltransferase Activity Causes Cancer Vulnerability in NDRG2low Adult T-Cell Leukemia/Lymphoma. Int. J. Mol. Sci. 2024, 25, 2842. https://doi.org/10.3390/ijms25052842 |
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言語 |
en |
| bibliographic_information |
en : International Journal of Molecular Sciences
巻 25,
号 5,
p. 2842,
発行日 2024-02-29
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| 出版者 |
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出版者 |
MDPI AG |
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言語 |
en |
| ISSN |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
1422-0067 |
| item_10001_relation_14 |
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関連タイプ |
isVersionOf |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.3390/ijms25052842 |
| 権利 |
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権利情報 |
© 2024 by the authors. |
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言語 |
en |
| 出版タイプ |
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出版タイプ |
VoR |
Fulltext (3.8 MB)
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