Aurora kinases link chromosome segregation and cell division to cancer susceptibility

Cytokinesis arrest and multiple centrosomes in B cell chronic lymphocytic leukaemia

“…Down‐regulation of TP53 is known as one cause to bypass anaphase checkpoint and DNA damage response during mitosis exit, which under normal conditions is active and prevents cells from acquiring chromosomal aberrations. Moreover, reduced TP53 levels lead to multiple centrosomes and accumulation of cells in cytokinesis 26, 41. Reduced TP53 protein levels may contribute to the cytokinesis defect described in the present study, a notion supported by our finding that siRNA‐mediated knockdown of TP53 in healthy donor CD19+ cells led to an accumulation of cells arrested in cytokinesis.…”

“…Our data also indicate that centrosome aberrations in malignant cells can arise via mitotic defects. The described cytokinesis failure leading to cells that harbour supernumerary centrosomes resembles the findings described for overexpression of Plk1, Evi1, Aurora A and Aurora B 41, 44…”

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

“…These observations shed a light on the mechanism underlying tumorigenesis caused by Aurora-A overexpression. Numerous studies have revealed that Aurora-A plays important functions during normal mitosis (reviewed in Katayama et al, 2003;Crane et al, 2004;Ducat and Zheng, 2004;Meraldi et al, 2004). Loss of function mutations or RNA interference in genes encoding Aurora-related kinases induce abnormal mitotic phenotypes from yeast to higher eukaryotes (Bischoff and Plowman, 1999;Berdnik and Knoblich, 2002;Giet et al, 2002;Kufer et al, 2003).…”

“…Aurora-A is one of three serine/threonine kinases (A, B and C) that are evolutionally conserved and regulate mitotic progression in various organisms (reviewed in Katayama et al, 2003;Crane et al, 2004;Ducat and Zheng, 2004;Meraldi et al, 2004). Aurora-A is localized at the centrosome during interphase, translocated to the mitotic spindle in early mitotic phase and degraded after metaphase transition.…”

Chromosomes with delayed replication timing lead to checkpoint activation, delayed recruitment of Aurora B and chromosome instability

“…Survivin has an essential role in chromosome alignment (Lens et al, 2003) and is important during mitosis for proper localization of INCENP and Aurora B (reviewed by Carmena and Earnshaw, 2003). Aurora B, which phosphorylates histone H3 on serine 10, is important for chromosome condensation, and monitors chromosome biorientation during congression by sensing tension across the centromere established once sister kinetochores are attached to the opposite spindle poles (reviewed by Meraldi et al, 2004). Aurora B has also emerged as an important regulator of the spindle assembly checkpoint.…”