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Aurora B: hooking up with cyclin-dependent kinases.

Poon RY - Cell Cycle (2013)

View Article: PubMed Central - PubMed

Affiliation: Division of Life Science, Center for Cancer Research and State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong. rycpoon@ust.hk

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In this issue of “Cell Cycle,” Malumbres and colleagues examined the effects of Aurkb inactivation in mouse cells... As genetic ablation of Aurkb results in mitotic aberrations and lethality after implantation in mice, the authors made use of conditional knockout mouse embryonic fibroblasts and chemical inhibition to tackle the issue... These tantalizing results establish a linkage between Aurkb and another major cell cycle regulator, cyclin-dependent kinase, through the CDK inhibitor p21... The observation that the CDK inhibitor p21 is induced after Aurkb inactivation provides a possible mechanistic basis of the premature mitotic exit... Yet a conceptual obstacle for p21 in causing premature mitotic exit is that the canonical p21 pathway is well established to be involved in interphase arrest (such as after DNA damage)... Hence inhibition of Aurkb is expected to activates p53 and its downstream targets such as p21... In addition, it is conceivable that the mitotic stress induced after Aurkb inhibition can also lead to p53 activation... A somewhat unanticipated result of Trakala et al. is the pronounced effect of Aurkb-deficiency on interphase... Entry into S-phase from quiescence is delayed in Aurkb-deficient MEFs or after treatment with the Aurora kinase inhibitor ZM447439... A reduction of Aurkb in heterozygous mice also delays cell cycle entry after partial hepatectomy or skin wound healing... However, as Aurkb is degraded at the end of mitosis by APC/C-mediated ubiquitination, one has to speculate that the Aurkb present during interphase is adequate to suppress the accumulation of p53 and p21 during normal cell cycle... Although the biological significance of the regulation of p53-p21 axis by Aurkb remains to be defined, these observations suggest the possibility of a novel mechanism that regulates CDKs in both mitosis and interphase... In addition to the effects on the cell cycle, other consequences of p53 activation after the Aurkb inactivation will also be interesting for further investigation.

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Figure 1. A model of links between Aurkb and cyclin-dependent kinases.
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Figure 1: Figure 1. A model of links between Aurkb and cyclin-dependent kinases.


Aurora B: hooking up with cyclin-dependent kinases.

Poon RY - Cell Cycle (2013)

Figure 1. A model of links between Aurkb and cyclin-dependent kinases.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3646856&req=5

Figure 1: Figure 1. A model of links between Aurkb and cyclin-dependent kinases.

View Article: PubMed Central - PubMed

Affiliation: Division of Life Science, Center for Cancer Research and State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong. rycpoon@ust.hk

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

In this issue of “Cell Cycle,” Malumbres and colleagues examined the effects of Aurkb inactivation in mouse cells... As genetic ablation of Aurkb results in mitotic aberrations and lethality after implantation in mice, the authors made use of conditional knockout mouse embryonic fibroblasts and chemical inhibition to tackle the issue... These tantalizing results establish a linkage between Aurkb and another major cell cycle regulator, cyclin-dependent kinase, through the CDK inhibitor p21... The observation that the CDK inhibitor p21 is induced after Aurkb inactivation provides a possible mechanistic basis of the premature mitotic exit... Yet a conceptual obstacle for p21 in causing premature mitotic exit is that the canonical p21 pathway is well established to be involved in interphase arrest (such as after DNA damage)... Hence inhibition of Aurkb is expected to activates p53 and its downstream targets such as p21... In addition, it is conceivable that the mitotic stress induced after Aurkb inhibition can also lead to p53 activation... A somewhat unanticipated result of Trakala et al. is the pronounced effect of Aurkb-deficiency on interphase... Entry into S-phase from quiescence is delayed in Aurkb-deficient MEFs or after treatment with the Aurora kinase inhibitor ZM447439... A reduction of Aurkb in heterozygous mice also delays cell cycle entry after partial hepatectomy or skin wound healing... However, as Aurkb is degraded at the end of mitosis by APC/C-mediated ubiquitination, one has to speculate that the Aurkb present during interphase is adequate to suppress the accumulation of p53 and p21 during normal cell cycle... Although the biological significance of the regulation of p53-p21 axis by Aurkb remains to be defined, these observations suggest the possibility of a novel mechanism that regulates CDKs in both mitosis and interphase... In addition to the effects on the cell cycle, other consequences of p53 activation after the Aurkb inactivation will also be interesting for further investigation.

Show MeSH