Aurora-A kinase is essential for bipolar spindle formation and early development
Authors
Cowley, Dale O.Rivera-Pérez, Jaime A.
Schliekelman, Mark
He, Yizhou Joseph
Oliver, Trudy G.
Lu, Lucy
O'Quinn, Ryan
Salmon, E. D.
Magnuson, Terry
Van Dyke, Terry
UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2009-02-17Keywords
AllelesAnimals
Apoptosis
Blastocyst
Cell Proliferation
Embryo Loss
Embryo, Mammalian
*Embryonic Development
Female
Fibroblasts
Gene Deletion
Gene Targeting
Mice
Mitosis
Mitotic Spindle Apparatus
Mutation
Ploidies
Pregnancy
Protein-Serine-Threonine Kinases
Cell Biology
Metadata
Show full item recordAbstract
Aurora-A is a conserved kinase implicated in mitotic regulation and carcinogenesis. Aurora-A was previously implicated in mitotic entry and spindle assembly, although contradictory results prevented a clear understanding of the roles of Aurora-A in mammals. We developed a conditional null mutation in the mouse Aurora-A gene to investigate Aurora-A functions in primary cells ex vivo and in vivo. We show here that conditional Aurora-A ablation in cultured embryonic fibroblasts causes impaired mitotic entry and mitotic arrest with a profound defect in bipolar spindle formation. Germ line Aurora-A deficiency causes embryonic death at the blastocyst stage with pronounced cell proliferation failure, mitotic arrest, and monopolar spindle formation. Aurora-A deletion in mid-gestation embryos causes an increase in mitotic and apoptotic cells. These results indicate that murine Aurora-A facilitates, but is not absolutely required for, mitotic entry in murine embryonic fibroblasts and is essential for centrosome separation and bipolar spindle formation in vitro and in vivo. Aurora-A deletion increases apoptosis, suggesting that molecular therapies targeting Aurora-A may be effective in inducing tumor cell apoptosis. Aurora-A conditional mutant mice provide a valuable system for further defining Aurora-A functions and for predicting effects of Aurora-A therapeutic intervention.Source
Mol Cell Biol. 2009 Feb;29(4):1059-71. Epub 2008 Dec 15. Link to article on publisher's siteDOI
10.1128/MCB.01062-08Permanent Link to this Item
http://hdl.handle.net/20.500.14038/48783PubMed ID
19075002Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1128/MCB.01062-08