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| Status |
Public on Feb 16, 2024 |
| Title |
Identification of genes essential for the cell death induced by OSW-1 using the Genome-wide CRISPR-Cas9 knockout (GeCKO) screening |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
The Golgi stress response is an important cytoprotective system that enhances Golgi function in response to cellular demand, while cells damaged by prolonged Golgi stress undergo cell death. OSW-1, a natural compound with anticancer activity, potently inhibits OSBP that transports cholesterol and phosphatidylinositol-4-phosphate (PI4P) at contact sites between the endoplasmic reticulum and the Golgi apparatus. Previously, we reported that OSW-1 induces the Golgi stress response, resulting in Golgi stress- induced transcription and cell death. However, the underlying molecular mechanism has been unknown. To reveal the mechanism of a novel pathway of the Golgi stress response regulating transcriptional induction and cell death (the PI4P pathway), we performed a genome-wide knockout screen and found that transcriptional induction as well as cell death induced by OSW-1 was repressed by the loss of regulators of PI4P synthesis, such as PITPNB and PI4KB. Our data indicate that OSW-1 induces Golgi stress-dependent transcriptional induction and cell death through dysregulation of the PI4P metabolism in the Golgi.
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| Overall design |
OSW-1 is a natural anticancer compound and activates the Golgi stress response. To search for genes essential for the cell death induced by OSW-1, we performed the Genome-wide CRISPR-Cas9 knockout (GeCKO) screening using OSW-1-resistant HeLa cells.
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| Contributor(s) |
Sasaki K, Yoshida H, Watanabe Y |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Feb 16, 2024 |
| Last update date |
Feb 16, 2024 |
| Contact name |
Kanae Sasaki |
| E-mail(s) |
sasaki@sci.u-hyogo.ac.jp
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| Organization name |
University of Hyogo
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| Department |
Department of Molecular Biochemistry, Graduate School of Sciences
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| Street address |
3-2-1 Kouto
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| City |
Kamigori-cho, Ako-gun |
| State/province |
Hyogo |
| ZIP/Postal code |
678-1297 |
| Country |
Japan |
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| Platforms (1) |
| GPL17303 |
Ion Torrent Proton (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA1077328 |
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