p53: guardian of ploidy

Abstract

Aneuploidy, often preceded by tetraploidy, is one of the hallmarks of solid tumors. Indeed, both aneuploidy and tetraploidy are oncogenic occurrences that are sufficient to drive neoplastic transformation and cancer progression. True to form, the tumor suppressor p53 obstructs propagation of these dangerous chromosomal events by either instigating irreversible cell cycle arrest or apoptosis. The tumor suppressor Lats2, along with other tumor inhibitory proteins such as BRCA1/2 and BubR1, are central to p53-dependent elimination of tetraploid cells. Not surprisingly, these proteins are frequently inactivated or downregulated in tumors, synergizing with p53 inactivation to establish an atmosphere of "tolerance" for a non-diploid state.

Figure 1

Schematic representation of the steps leading to, or avoiding, aneuploidy. Wild type p53 function is crucial for the elimination of tetraploid cells from the replicating pool. Loss of p53 and p73 tumor suppressors facilitates aneuploid tumor formation. Orange boxes represent proliferation “stops”, whereas green represents proliferation “go”.