Perturbations in cell cycle are known to induce

Perturbations in akt pathway are known to induce apoptosis. Our results show that a fraction of the DT40YB-1b+/− cells, in addition to becoming tetraploids, undergo apoptotic cell death. Similar observations linking polyploidy and apoptosis have been made in the past [23], [30], [31], [32], [33], [34]. Interference with the expression or function of survivin, an inhibitor of apoptosis, has been shown to cause caspase-dependent cell death during the G2/M phase of the cell cycle, centrosome dysregulation, multipolar mitotic spindles, and multinucleate polyploid cells [34]. It is interesting to note here that the cyclin-dependent kinase inhibitor p21, whose expression is elevated in DT40YB-1b+/− cells, is known to form a ternary complex with survivin and caspase-3 within centrosomes. Interestingly, microarray analysis revealed a drastic reduction in the levels of p21 and replication factor C40-kDa subunit in mutant cells compared to wild-type. It is likely that these cdk inhibitors are responsible for the observed effects in heterozygous mutant cells. Further experiments are necessary to understand the mechanism of action of YB-1 in cell cycle.
Acknowledgements