Cep55 stabilization is required for normal execution of cytokinesis

Armando van der Horst, Jacinta Simmons and Kum Kum Khanna (2009) Cep55 stabilization is required for normal execution of cytokinesis. Cell Cycle, 8 22: 3742-3749. doi:10.4161/cc.8.22.10047


Author Armando van der Horst
Jacinta Simmons
Kum Kum Khanna
Title Cep55 stabilization is required for normal execution of cytokinesis
Formatted title
Cep55 stabilization is required for normal execution of cytokinesis
Journal name Cell Cycle   Check publisher's open access policy
ISSN 1538-4101
Publication date 2009-11-15
Year available 2009
Sub-type Article (original research)
DOI 10.4161/cc.8.22.10047
Volume 8
Issue 22
Start page 3742
End page 3749
Total pages 8
Editor Mikhail V Blagosklonny
Place of publication United States
Publisher Landes Bioscience
Collection year 2010
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
0601 Biochemistry and Cell Biology
Abstract Cep55 is a mitotic phosphoprotein that plays an important role in cytokinesis, the final stage of cell division during which physical separation of the two daughter cells is accomplished. We recently demonstrated that the peptidyl-prolyl isomerase Pin1 regulates this cell cycle event by enhancing the Plk1-dependent phosphorylation of Cep55. We show here that Cep55 is stabilized post-translationally during mitosis and that siRNA-mediated knockdown of Pin1 prevents this stabilization. Consistent with this, Cep55 is unstable in Pin1 knockout mouse embryonic fibroblasts. Moreover, mutation of the Pin1 binding sites in Cep55 reduces its stability during mitosis. Mutation of the Plk1 phosphorylation site also lowers Cep55 stability, whereas overexpression of Plk1 increases Cep55 levels, in keeping with Pin1 regulating Plk1-mediated phosphorylation of Cep55. Importantly, expression of wild-type Cep55 at levels similar to that of the phosphorylation mutants only partially reverts the cytokinesis defect induced by depletion of Cep55, indicating that inadequate levels of Cep55 prevent proper execution of cytokinesis. Taken together, these data provide more insight into the regulation of the final stages of cell division. As cytokinesis defects can cause chromosomal instability, knowledge about the processes that regulate normal cytokinesis adds to our understanding of events that lead to tumorigenesis.
Formatted abstract
Cep55 is a mitotic phosphoprotein that plays an important role in cytokinesis, the final stage of cell division during which physical separation of the two daughter cells is accomplished. We recently demonstrated that the peptidyl-prolyl isomerase Pin1 regulates this cell cycle event by enhancing the Plk1-dependent phosphorylation of Cep55. We show here that Cep55 is stabilized post-translationally during mitosis and that siRNA-mediated knockdown of Pin1 prevents this stabilization. Consistent with this, Cep55 is unstable in Pin1 knockout mouse embryonic fibroblasts. Moreover, mutation of the Pin1 binding sites in Cep55 reduces its stability during mitosis. Mutation of the Plk1 phosphorylation site also lowers Cep55 stability, whereas overexpression of Plk1 increases Cep55 levels, in keeping with Pin1 regulating Plk1-mediated phosphorylation of Cep55. Importantly, expression of wild-type Cep55 at levels similar to that of the phosphorylation mutants only partially reverts the cytokinesis defect induced by depletion of Cep55, indicating that inadequate levels of Cep55 prevent proper execution of cytokinesis. Taken together, these data provide more insight into the regulation of the final stages of cell division. As cytokinesis defects can cause chromosomal instability, knowledge about the processes that regulate normal cytokinesis adds to our understanding of events that lead to tumorigenesis.

Q-Index Code C1
Q-Index Status Provisional Code

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Wed, 31 Mar 2010, 01:02:50 EST by Amanda Jones on behalf of Medicine - Royal Brisbane and Women's Hospital