Protein kinase CK2 is involved in G2 arrest and apoptosis following spindle damage in epithelial cells

p53 undergoes phosphorylation on several residues in response to cellular s tresses that include UV and ionizing radiation, however the influence of sp indle damage on this parameter is relatively unclear. Consequently, the eff ect of nocodazole on serine 392 phosphorylation was examined in two epithel ial cell lines. We show that this process is dependent upon the stepwise ac tivation of p38 mitogen-activated protein kinase (p38 MAPK) and protein kin ase casein kinase 2 (CK2). Furthermore, this activation correlated with the biochemical regulation of the maturation-promoting factor (MPF, cdc2/cycli n B), as both DRB and antisense depletion of CK2, as well as SB203580 were associated with an inhibition of its activation in response to nocodazole. Strikingly, when the cell cycle characteristics of nocodazole treated cells were examined, we observed that depletion or inhibition of the catalytic s ubunit of CK2, in the presence of microtubule inhibitors, resulted in a com promise of the G2 arrest (spindle checkpoint). Furthermore, CK2-depleted, n ocodazole treated cells demonstrated a dramatic reduction in the apoptotic cell fraction, confirming that these cells had been endowed with oncogenic properties. These changes were observed in both HeLa cells and HCT116 cells . We also show that this effect is dependent on the presence of functional wild-type p53, as this phenomenon is not apparent in HCT116 p53 /(-) cells. Collectively, our results indicate two novel roles for CK2 in the spindle checkpoint arrest, in concert with p53. Firstly, to maintain increased cycl inB/cdc2 kinase activity, as a component of G2 arrest, and secondly, a role in p53-mediated apoptosis. These findings may have implications for an imp roved understanding of abnormalities of the spindle checkpoint in human can cers, which is a prerequisite for defining future therapies.