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| Verfasst von: | Abu-Odeh, Mohammad [VerfasserIn]  |
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| | Salah, Zaidoun [VerfasserIn] |
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| | Herbel, Christoph [VerfasserIn] |
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| | Hofmann, Thomas G. [VerfasserIn] |
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| | Aqeilan, Rami I. [VerfasserIn] |
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| Titel: | WWOX, the common fragile site FRA16D gene product, regulates ATM activation and the DNA damage response |
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| Verf.angabe: | Mohammad Abu-Odeh, Zaidoun Salah, Christoph Herbel, Thomas G. Hofmann, and Rami I. Aqeilan |
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| E-Jahr: | 2014 |
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| Jahr: | October 20, 2014 |
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| Umfang: | 10 S. |
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| Fussnoten: | Gesehen am 01.12.2020 |
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| Titel Quelle: | Enthalten in: National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America |
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| Ort Quelle: | Washington, DC : National Acad. of Sciences, 1915 |
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| Jahr Quelle: | 2014 |
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| Band/Heft Quelle: | 111(2014), 44, Seite E4716-E4725 |
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| ISSN Quelle: | 1091-6490 |
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| Abstract: | Genomic instability is a hallmark of cancer. The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor spanning the common chromosomal fragile site FRA16D. Here, we report a direct role of WWOX in DNA damage response (DDR) and DNA repair. We show that Wwox deficiency results in reduced activation of the ataxia telangiectasia-mutated (ATM) checkpoint kinase, inefficient induction and maintenance of γ-H2AX foci, and impaired DNA repair. Mechanistically, we show that, upon DNA damage, WWOX accumulates in the cell nucleus, where it interacts with ATM and enhances its activation. Nuclear accumulation of WWOX is regulated by its K63-linked ubiquitination at lysine residue 274, which is mediated by the E3 ubiquitin ligase ITCH. These findings identify a novel role for the tumor suppressor WWOX and show that loss of WWOX expression may drive genomic instability and provide an advantage for clonal expansion of neoplastic cells. |
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| DOI: | doi:10.1073/pnas.1409252111 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1073/pnas.1409252111 |
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| | Volltext: https://www.pnas.org/content/111/44/E4716 |
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| | DOI: https://doi.org/10.1073/pnas.1409252111 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | ataxia telangiectasia-mutated |
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| | common fragile sites |
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| | genomic instability |
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| | ITCH |
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| | WW domain-containing oxidoreductase |
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| K10plus-PPN: | 1741630428 |
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| Verknüpfungen: | → Zeitschrift |
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WWOX, the common fragile site FRA16D gene product, regulates ATM activation and the DNA damage response / Abu-Odeh, Mohammad [VerfasserIn]; October 20, 2014 (Online-Ressource)
