Aurora-A — A guardian of poles

Abstract

The three human homologues of Aurora kinases (A, B and C) are essential for proper execution of various mitotic events and are important for maintaining genomic integrity. Aurora-A is mainly localized at spindle poles and the mitotic spindle during mitosis, where it regulates the functions of centrosomes, spindles and kinetochores required for proper mitotic progression. Recent studies have revealed that Aurora-A is frequently overexpressed in various cancer cells, indicating its involvement in tumorigenesis. What are the normal physiological roles of Aurora-A, how are these regulated and how might the enzyme function during tumorigenesis?

Identification of genes that confer tumor cell resistance to the Aurora B kinase inhibitor, AZD1152

“…1,2 Aurora A localizes to spindle poles and has a crucial role in bipolar spindle formation. 3 Aurora B, a chromosome passenger protein, localizes to centromeres in early mitosis and then the spindle midzone in anaphase, and is required for mitotic histone H3 phosphorylation, chromosome biorientation, the spindle assembly checkpoint and cytokinesis. 4 Aurora C is also a chromosomal passenger protein and, in normal cells, its expression is restricted to the testis where it functions primarily in male gametogenesis.…”

AIP regulates stability of Aurora-A at early mitotic phase coordinately with GSK-3β

“…Aurora-A is a mitotic kinase that plays critical roles in the centrosome cycle and spindle assembly (Meraldi et al, 2004;Marumoto et al, 2005). APC/C regulates Aurora-A stability as cells progress from metaphase.…”

“…Aurora-A is a mitotic kinase that plays critical roles in the centrosome cycle, spindle assembly and chromosome segregation (Meraldi et al, 2004;Marumoto et al, 2005). The protein level of Aurora-A is temporally regulated by ubiquitin-dependent proteolysis at the end of mitosis, before cells progress into the G 1 phase of the next cell cycle.…”

“…Aurora-A is located in the chromosome 20q13 region, a region that is frequently amplified in breast cancers and in diverse cancer cell lines. Overexpression of Aurora-A in primary human tumors indeed correlates with poor prognosis and invasiveness (Marumoto et al, 2005).…”

Response to MLN8237 in Pancreatic Cancer Is Not Dependent on RalA Phosphorylation

“…A number of proteins associated with mitosis are phosphorylated by AAK through spatially and temporally controlled mechanisms (13). Amplification of the AURKA gene is commonly found in a number of malignancies (14–16) and overexpression of AAK is associated with high tumor grade and poor prognosis (15, 17–20).…”