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SCFFbxw5 mediates transient degradation of actin remodeler Eps8 to allow proper mitotic progression

Eps8, a bi-functional actin cytoskeleton remodeler, is a positive regulator of cell proliferation and motility. Here, we describe an unrecognized mechanism regulating Eps8 that is required for proper mitotic progression: While Eps8 is stable in G1 and S phase, its half-life drops sharply in G2. This...

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Bibliographische Detailangaben
Hauptverfasser: Werner, Achim (VerfasserIn) , Reifenberger, Nina (VerfasserIn) , Habeck, Gregor (VerfasserIn) , Becker, Janina (VerfasserIn) , Lorenz, Holger (VerfasserIn) , Melchior, Frauke (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2013 August 21
In: Nature cell biology
Year: 2013, Jahrgang: 15, Heft: 2, Pages: 179-188
ISSN:1476-4679
DOI:10.1038/ncb2661
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1038/ncb2661
Verlag, Volltext: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749308/
Volltext
Verfasserangaben:Achim Werner, Andrea Disanza, Nina Reifenberger, Gregor Habeck, Janina Becker, Matthew Calabrese, Henning Urlaub, Holger Lorenz, Brenda Schulman, Giorgio Scita, and Frauke Melchior
Beschreibung
Zusammenfassung:Eps8, a bi-functional actin cytoskeleton remodeler, is a positive regulator of cell proliferation and motility. Here, we describe an unrecognized mechanism regulating Eps8 that is required for proper mitotic progression: While Eps8 is stable in G1 and S phase, its half-life drops sharply in G2. This requires G2-specific proteasomal degradation mediated by the Ubiquitin E3 ligase SCFFbxw5. Consistent with a short window of degradation, Eps8 disappears from the cell cortex early in mitosis, but reappears at the midzone of dividing cells. Failure to reduce Eps8 levels in G2 prolongs its localization at the cell cortex and markedly delays cell rounding and prometaphase duration. However, during late stages of mitosis and cytokinesis, Eps8 capping activity is required to prevent membrane blebbing and cell shape deformations. Our findings identify SCFFbxw5-driven fluctuation of Eps8 levels as an important mechanism that contributes to cell-shape changes during entry into - and exit from - mitosis.
Beschreibung:"Fbxw5" erscheint kleiner gedruckt und hochgestellt
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Beschreibung:Online Resource
ISSN:1476-4679
DOI:10.1038/ncb2661

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