Aurora B is a mitotic checkpoint kinase that plays a pivotal role in the cell 
cycle, ensuring correct chromosome segregation and normal progression through 
mitosis. Aurora B is overexpressed in many types of human cancers, which has 
made it an attractive target for cancer therapies. Tumor suppressor p53 is a 
genome guardian and important negative regulator of the cell cycle. Whether 
Aurora B and p53 are coordinately regulated during the cell cycle is not known. 
We report that Aurora B directly interacts with p53 at different subcellular 
localizations and during different phases of the cell cycle (for instance, at 
the nucleus in interphase and the centromeres in prometaphase of mitosis). We 
show that Aurora B phosphorylates p53 at S183, T211, and S215 to accelerate the 
degradation of p53 through the polyubiquitination-proteasome pathway, thus 
functionally suppressing the expression of p53 target genes involved in cell 
cycle inhibition and apoptosis (e.g., p21 and PUMA). Pharmacologic inhibition of 
Aurora B in cancer cells with WT p53 increased p53 protein level and expression 
of p53 target genes to inhibit tumor growth. Together, these results define a 
mechanism of p53 inactivation during the cell cycle and imply that oncogenic 
hyperactivation or overexpression of Aurora B may compromise the tumor 
suppressor function of p53. We have elucidated the antineoplastic mechanism for 
Aurora B kinase inhibitors in cancer cells with WT p53.