Overproduction of hCdc14A leads to progressive cell death, accompanied by accumulation of pre-G1 DNA fragments and gradual elimination of cells at the G2/M transition. In 50% of the mitotic cells, multipolar mitotic spindles and misaggregated chromosomes are found. hCdc14A localizes to the centrosomes at the cell-cycle interphase stage. When the cell enters mitosis, this localization disappears suggesting that hCdc14A dissociates from the centrosomes at the G2/M transition. hCdc14A localizes to interphase centrosomes, but not to mitotic centrosomes, while hCdc14B localizes to the interphase nucleolus. Thus each isoform regulates separate cell cycle events. Cdc14A may affect cell cycle progression by its ability to dephosphorylate p53 at Ser315. This phosphatase activity is mediated by the interaction between the N-terminus of hCdc14A and the C-terminus of p53.