AuroraA overexpression overrides the mitotic spindle checkpoint triggered by nocodazole, a microtubule destabilizer (original) (raw)
Related papers
Chromosome dynamics: new light on Aurora B kinase function
Current biology, 2002
Aurora B family kinases play an essential role in chromosome segregation and cytokinesis. Recent work suggests that the kinase activity is required for bipolar chromosome orientation, kinetochore assembly, spindle checkpoint and microtubule dynamics. Aurora B also has additional functions in chromosome condensation and cohesion.
The Journal of Cell Biology, 2001
Aurora/Ipl1-related kinases are a conserved family of enzymes that have multiple functions during mitotic progression. Although it has been possible to use conventional genetic analysis to dissect the function of aurora , the founding family member in Drosophila (Glover, D.M., M.H. Leibowitz, D.A. McLean, and H. Parry. 1995. Cell . 81:95-105), the lack of mutations in a second aurora-like kinase gene, aurora B , precluded this approach. We now show that depleting Aurora B kinase using double-stranded RNA interference in cultured Drosophila cells results in polyploidy. aurora B encodes a passenger protein that associates first with condensing chromatin, concentrates at centromeres, and then relocates onto the central spindle at anaphase. Cells depleted of the Aurora B kinase show only partial chromosome condensation at mitosis. This is associated with a reduction in levels of the serine 10 phosphorylated form of histone H3 and a failure to recruit the Barren condensin protein onto chromosomes. These defects are associated with abnormal segregation resulting from lagging chromatids and extensive chromatin bridging at anaphase, similar to the phenotype of barren mutants (Bhat, M.A., A.V. . Cell . 87:1103-1114. The majority of treated cells also fail to undertake cytokinesis and show a reduced density of microtubules in the central region of the spindle. This is accompanied by a failure to correctly localize the Pavarotti kinesinlike protein, essential for this process. We discuss these conserved functions of Aurora B kinase in chromosome transmission and cytokinesis.
Aurora-A Kinase Is Essential for Bipolar Spindle Formation and Early Development
Molecular and Cellular Biology, 2009
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.
PLoS genetics, 2014
Aurora B kinase (AURKB) is the catalytic subunit of the chromosomal passenger complex (CPC), an essential regulator of chromosome segregation. In mitosis, the CPC is required to regulate kinetochore microtubule (K-MT) attachments, the spindle assembly checkpoint, and cytokinesis. Germ cells express an AURKB homolog, AURKC, which can also function in the CPC. Separation of AURKB and AURKC function during meiosis in oocytes by conventional approaches has not been successful. Therefore, the meiotic function of AURKC is still not fully understood. Here, we describe an ATP-binding-pocket-AURKC mutant, that when expressed in mouse oocytes specifically perturbs AURKC-CPC and not AURKB-CPC function. Using this mutant we show for the first time that AURKC has functions that do not overlap with AURKB. These functions include regulating localized CPC activity and regulating chromosome alignment and K-MT attachments at metaphase of meiosis I (Met I). We find that AURKC-CPC is not the sole CPC c...
Mitotic requirement for aurora A kinase is bypassed in the absence of aurora B kinase
FEBS Letters, 2005
We investigated why treatment of cells with dual aurora A and B kinase inhibitors produces phenotypes identical to inactivation of aurora B. We found that dual aurora kinase inhibitors in fact potently inhibit cellular activities of both kinases, indicating that inactivation of aurora B bypasses aurora A in mitosis. RNAi experiments further established that inactivation of aurora B indeed bypasses the requirement for aurora A and leads to polyploidy. Inactivation of aurora A activates checkpoint kinase BubR1 in an aurora B-dependent manner. Our results thus show that aurora B is responsible for mitotic arrest in the absence of aurora A.
Aurora B Regulates MCAK at the Mitotic Centromere
Developmental Cell, 2004
that the Aurora B complex plays a critical role in estaband Jason R. Swedlow 1 lishing bipolar chromosome attachment and that this 1 Division of Gene Regulation and Expression function is highly conserved. 2 MRC Protein Phosphorylation Unit Aurora B, INCENP, and survivin all behave as chromo-Wellcome Trust Biocentre some passenger proteins, localizing between sister cen-University of Dundee tromeres in the inner centromere from late G2 through Dow Street to metaphase (Andrews et al., 2003; Carmena and Earn-Dundee DD1 5EH shaw, 2003). As chromosome segregation initiates, the United Kingdom complex leaves the inner centromere and concentrates 3 Department of Physiology and Biophysics on central spindle microtubules where it functions in University of Washington School of Medicine cytokinesis. In yeast, the Aurora B/Ipl1p complex phos-1959 N.E. Pacific Street phorylates a number of inner and outer kinetochore pro-Seattle, Washington 98195 teins (Biggins et al., 1999; Cheeseman et al., 2002; Westermann et al., 2003). Aurora B also phosphorylates the centromere-specific histone H3 variant CENP-A (Zeitlin Summary et al., 2001), as well as histone H3 localized throughout the chromosome (Hsu et al., 2000; Murnion et al., 2001).