Guerra 20_9

Protein kinase CK2 is a highly conserved serine/ threonine kinase ubiquitously distributed in all investigated eukaryotes and involved in several intracellular pathways which control, among others, cell cycle, proliferation, apoptosis and transformation. Similarly, the PI3K-AKT pathway deregulation has been shown to play an important role in tumor development and tumor response to anti-cancer treatment. In this study, it is shown that the specific inhibition of the PI3KAKT signaling pathway in combination with depletion of CK2 subunits by antisense oligodeoxynucleotides leads to an enhanced drug-induced apoptotic response. Moreover, in vitro as well as in vivo studies show that the individual CK2 subunits interact with AKT kinase and that the complex formation is not modulated by the phosphorylation status of AKT. Furthermore, the fact that the interaction between CK2 subunits and AKT enhances AKT kinase activity identifies a novel molecular mechanism that leads to modulation of AKT activation raising the possibility that CK2 and AKT might be implicated in common pathways that control cell proliferation and survival.