Roles of aurora‐A kinase in mitotic entry and G2 checkpoint in mammalian cells

Abstract

Background : Various mitotic events are controlled by Cdc2-cyclin B and other mitotic kinases. Aurora/ Ipl1-related mitotic kinases were proved to play key roles in mitotic progression in diverse lower organisms. Aurora-A is a mammalian counterpart of aurora/Ipl1-related kinases and is thought to be a potential oncogene. However, the regulation of aurora-A activation and the commitment of aurora-A in the progression of G2-M phase are largely unknown in mammalian cells.

Overexpression of aurora kinase A in mouse mammary epithelium induces genetic instability preceding mammary tumor formation

“…Aurora-A is localized at the centrosome during interphase, translocated to the mitotic spindle in early mitotic phase and degraded after metaphase transition. It has been demonstrated that activation of Aurora-A is required for mitotic entry, centrosome maturation and separation and G2 to M transition (Marumoto et al, 2002;Meraldi et al, 2002;Anand et al, 2003;Hirota et al, 2003;Giet et al, 2005). Overexpression of Aurora-A also results in defective spindle assembly checkpoint, allowing cells with abnormal chromosomal separation to enter anaphase, leading to aneuploidy (Zhou et al, 1998;Stenoien et al, 2003).…”

RASSF1A interacts with and activates the mitotic kinase Aurora-A

“…Aurora-A is important in centrosome maturation and separation as well as in spindle assembly (Andrews et al, 2003;Carmena and Earnshaw, 2003;Marumoto et al, 2005). Moreover, activity of Aurora-A is required for timely mitotic entry (Marumoto et al, 2002Hirota et al, 2003;Hachet et al, 2007;Portier et al, 2007). Both upregulation and downregulation of Aurora-A results in cytokinesis failure Anand et al, 2003;Marumoto et al, 2003;Zhang et al, 2004), indicating that the timing of Aurora-A activity is important for proper cytokinesis.…”

Targeted disruption of Aurora A causes abnormal mitotic spindle assembly, chromosome misalignment and embryonic lethality

“…Identification of microtubule-associated proteins as substrates of Aurora A (Yu et al, 2005;Koffa et al, 2006) as well as their localization on k fibers in prometaphase human cells (Sillje et al, 2006) indicates that Aurora A forms complex with mitotic spindle assembly factors in the organization of the spindle microtubules. Additionally, while silencing of Aurora A has been reported to cause delay or block in mitotic entry (Marumoto et al, 2002;Hirota et al, 2003;Du and Hannon, 2004;Satinover et al, 2006), accelerated initiation of mitosis in presence of active Aurora A has also been observed (Ma et al, 2003;Liu and Ruderman, 2006). These effects may, in part, be explained by the reported role of Aurora A in facilitating expression and activation of critical mitosis regulators cyclin B and Cdc25B (Mendez et al, 2000;Tay et al, 2000;Dutertre et al, 2004).…”