title: SCFFbxw5 mediates transient degradation of actin remodeller Eps8 to allow proper mitotic progression.
abstract: 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(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(Fbxw5)-driven fluctuation of Eps8 levels as an important mechanism that contributes to cell-shape changes during entry into-and exit from-mitosis.
authors: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Germany. a.werner@berkeley.edu
authors: Achim
authors: A
authors: Werner
authors: Andrea
authors: A
authors: Disanza
authors: Nina
authors: N
authors: Reifenberger
authors: Gregor
authors: G
authors: Habeck
authors: Janina
authors: J
authors: Becker
authors: Matthew
authors: M
authors: Calabrese
authors: Henning
authors: H
authors: Urlaub
authors: Holger
authors: H
authors: Lorenz
authors: Brenda
authors: B
authors: Schulman
authors: Giorgio
authors: G
authors: Scita
authors: Frauke
authors: F
authors: Melchior
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D048430:Cell Shape; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints; D057809:HEK293 Cells; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D008677:Metaphase; D051379:Mice; D018345:Mice, Knockout; D018715:Microscopy, Video; D008938:Mitosis; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D055550:Protein Stability; D059748:Proteolysis; D034622:RNA Interference; D013997:Time Factors; D014162:Transfection; D054875:Ubiquitination
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C489989:EPS8 protein, human; C083430:Eps8 protein, mouse; D044783:F-Box Proteins; C528759:FBXW5 protein, human; D046988:Proteasome Endopeptidase Complex