TAp73α binds the kinetochore proteins Bub1 and Bub3 resulting in polyploidy

Aneuploidy is a characteristic of most solid tumors, often associated with negative prognosis. It can arise from two principal mechanisms: from a tetraploid intermediate state, or directly from errors at cell division. The control of cell division, crucial to maintain genomic stability, is still poorly understood in its relationship to aneuploidy. Here we show that the TAp73α isoform induces polyploidy when over-expressed. This is possibly due to the interaction of TAp73α with kinetochore-related proteins leading to the alteration of mitotic checkpoint abilities. TAp73α but not p53 or any of the other p73 isoforms binds Bub1 and Bub3. Since TAp73α is frequently over-expressed in cancer, this interaction may contribute to the aneuploidy observed in cancer progression. Our results suggest a novel molecular mechanism leading to aneuploidy involving interference of TAp73α with Bub1 and Bub3 resulting in an altered mitotic checkpoint.