mediates transient degradation of actin remodeller Eps8 to allow proper mitotic progression

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

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Bibliographic Details
Published inNature cell biology Vol. 15; no. 2; pp. 179 - 189
Main Authors Werner, Achim, Disanza, Andrea, Reifenberger, Nina, Habeck, Gregor, Becker, Janina, Calabrese, Matthew, Urlaub, Henning, Lorenz, Holger, Schulman, Brenda, Scita, Giorgio, Melchior, Frauke
Format Journal Article
LanguageEnglish
Published Nature Publishing Group 01.02.2013
Subjects
Actin
Genetic aspects
Mitosis
Physiological aspects
Italy
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Summary:Eps8, a bi-functional actin cytoskeleton remodeller, is a positive regulator of cell proliferation and motility. Here, we describe an unrecognized mechanism regulating Eps8 that is required for proper mitotic progression: whereas 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 [SCF.sup.Fbxw5]. 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 [SCF.sup.Fbxw5]-driven fluctuation of Eps8 levels as an important mechanism that contributes to cell-shape changes during entry into--and exit from--mitosis.
ISSN:1465-7392
1476-4679
DOI:10.1038/ncb2661