ID | 115922 |
Author |
Hashimoto, Eiichi
The University of Tokyo
Okuno, Shota
The University of Tokyo
Hirayama, Shoshiro
The University of Tokyo
Arata, Yoshiyuki
The University of Tokyo
Goto, Tsuyoshi
The University of Tokyo
Kosako, Hidetaka
Tokushima University
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Hamazaki, Jun
The University of Tokyo
Murata, Shigeo
The University of Tokyo
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Content Type |
Journal Article
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Description | The proteasome is a therapeutic target in cancer, but resistance to proteasome inhibitors often develops owing to the induction of compensatory pathways. Through a genome-wide siRNA screen combined with RNA sequencing analysis, we identified hexokinase and downstream O-GlcNAcylation as cell survival factors under proteasome impairment. The inhibition of O-GlcNAcylation synergistically induced massive cell death in combination with proteasome inhibition. We further demonstrated that O-GlcNAcylation was indispensable for maintaining proteasome activity by enhancing biogenesis as well as proteasome degradation in a manner independent of Nrf1, a well-known compensatory transcription factor that upregulates proteasome gene expression. Our results identify a pathway that maintains proteasome function under proteasome impairment, providing potential targets for cancer therapy.
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Journal Title |
iScience
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ISSN | 25890042
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Publisher | Elsevier
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Volume | 23
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Issue | 7
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Start Page | 101299
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Published Date | 2020-07-24
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Rights | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
Publisher
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departments |
Institute of Advanced Medical Sciences
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