Document Detail

SCFFbxw5 mediates transient degradation of actin remodeller Eps8 to allow proper mitotic progression.
MedLine Citation:
PMID:  23314863     Owner:  NLM     Status:  MEDLINE    
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.
Achim Werner; Andrea Disanza; Nina Reifenberger; Gregor Habeck; Janina Becker; Matthew Calabrese; Henning Urlaub; Holger Lorenz; Brenda Schulman; Giorgio Scita; Frauke Melchior
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-13
Journal Detail:
Title:  Nature cell biology     Volume:  15     ISSN:  1476-4679     ISO Abbreviation:  Nat. Cell Biol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-04     Completed Date:  2013-03-29     Revised Date:  2013-08-27    
Medline Journal Info:
Nlm Unique ID:  100890575     Medline TA:  Nat Cell Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  179-88     Citation Subset:  IM    
Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Germany.
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MeSH Terms
Actin Cytoskeleton / metabolism*
Adaptor Proteins, Signal Transducing / genetics,  metabolism*
Binding, Competitive
Cell Shape*
F-Box Proteins / genetics,  metabolism*
G2 Phase Cell Cycle Checkpoints
HEK293 Cells
HeLa Cells
Mice, Knockout
Microscopy, Video
Proteasome Endopeptidase Complex / metabolism
Protein Binding
Protein Stability
RNA Interference
Time Factors
Grant Support
268836//European Research Council; 2R01GM069530/GM/NIGMS NIH HHS; P30 CA021765/CA/NCI NIH HHS; R01 GM069530/GM/NIGMS NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/EPS8 protein, human; 0/Eps8 protein, mouse; 0/F-Box Proteins; 0/FBXW5 protein, human; EC Endopeptidase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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