Aurora-A Kinase Is Essential for Bipolar Spindle Formation and Early Development

被引：105

作者：

Cowley, Dale O. ^{[1
,2
]}

Rivera-Perez, Jaime A. ^{[3
]}

Schliekelman, Mark ^{[4
]}

He, Yizhou Joseph ^{[4
]}

Oliver, Trudy G. ^{[1
,2
]}

Lu, Lucy ^{[1
,2
]}

O'Quinn, Ryan ^{[5
]}

Salmon, E. D. ^{[5
]}

Magnuson, Terry ^{[3
]}

Van Dyke, Terry ^{[1
,2
]}

机构：

[1] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[3] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA

[4] Univ N Carolina, Curriculum Genet, Chapel Hill, NC 27599 USA

[5] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2009年 / 29卷 / 04期

关键词：

UBIQUITIN-PROTEASOME PATHWAY; SMALL-MOLECULE INHIBITOR; MITOTIC ENTRY; CHROMOSOME SEGREGATION; B-KINASE; CAENORHABDITIS-ELEGANS; PROTEIN-KINASE; HISTONE H3; MICROTUBULE ATTACHMENT; CENTROSOME MATURATION;

D O I：

10.1128/MCB.01062-08

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1059 / 1071

页数：13