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http://hdl.handle.net/2445/178607
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DC Field | Value | Language |
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dc.contributor.author | Sato, Mai | - |
dc.contributor.author | Rodriguez Barrueco, Ruth | - |
dc.contributor.author | Yu, Jiyang | - |
dc.contributor.author | Do, Catherine | - |
dc.contributor.author | Silva, Jose M. | - |
dc.contributor.author | Gautier, Jean | - |
dc.date.accessioned | 2021-06-21T17:01:18Z | - |
dc.date.available | 2021-06-21T17:01:18Z | - |
dc.date.issued | 2014-12-26 | - |
dc.identifier.issn | 1949-2553 | - |
dc.identifier.uri | http://hdl.handle.net/2445/178607 | - |
dc.description.abstract | MYC deregulation is a driver of many human cancers. Altering the balance of MYC protein levels at the level of transcription, protein stability, or turnover is sufficient to transform cells to a tumorigenic phenotype. While direct targeting of MYC is difficult, specific genetic vulnerabilities of MYC-deregulated cells could be exploited to selectively inhibit their growth. Using a genome-wide shRNA screen, we identified 78 candidate genes, which are required for survival of human mammary epithelial cells with elevated MYC levels. Among the candidates, we validated and characterized FBXW7, a component of the SCF-like ubiquitin ligase complex that targets MYC for proteasomal degradation. Down-regulation of FBXW7 leads to synergistic accumulation of cellular and active chromatin-bound MYC, while protein levels of other FBXW7 targets appear unaffected. Over a four-week time course, continuous FBXW7 down-regulation and MYC activation together cause an accumulation of cells in S-phase and G2/M-phase of the cell cycle. Under these conditions, we also observe elevated chromatin-bound levels of CDC45, suggesting increased DNA replication stress. Consistent with these results, FBXW7 down-regulation alone decreases the survival of T47D breast cancer cells. These results establish that FBXW7 down-regulation is synthetic lethal with MYC, and that MYC is a critical target of FBXW7 in breast epithelial cells. | - |
dc.format.extent | 14 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Impact Journals | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.3203 | - |
dc.relation.ispartof | Oncotarget, 2014, vol. 6, num. 5, p. 3292-3305 | - |
dc.relation.uri | https://doi.org/10.18632/oncotarget.3203 | - |
dc.rights | cc-by (c) Sato, Mai et al., 2014 | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.source | Articles publicats en revistes (Patologia i Terapèutica Experimental) | - |
dc.subject.classification | Càncer | - |
dc.subject.classification | Proteïnes | - |
dc.subject.classification | Cèl·lules | - |
dc.subject.other | Cancer | - |
dc.subject.other | Proteins | - |
dc.subject.other | Cells | - |
dc.title | MYC is a critical target of FBXW7 | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 694978 | - |
dc.date.updated | 2021-06-21T17:01:18Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 25669969 | - |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) |
Files in This Item:
File | Description | Size | Format | |
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694978.pdf | 1.76 MB | Adobe PDF | View/Open |
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