Visit our Expo - Redox and Inflammation signaling 2012

Session III : Protein kinase cascades as therapeutic targets Poster III, 23
CK2 modulates AKT kinase activity: implication in cell survival and death
Barbara Guerra
Dep. of Biochemistry & Molecular Biology, University of Southern Denmark, DK-5230
Odense, Denmark. E-mail: bag@bmb.sdu.dk
Protein kinase CK2 is a Ser/Thr kinase ubiquitously distributed and highly conserved in all
eukaryotic organisms so far investigated. CK2 is implicated in many cellular functions e.g.
cell growth, cell cycle progression, transformation and cell survival. Mounting evidence has
indicated that CK2 is also implicated in cancer. For instance, a potent biological synergy in
the development of primitive multiclonal lymphoid leukemias has been observed in bitransgenic
mice overexpressing CK2alpha-catalytic subunit and c-Myc. Accelerated
lymphomagenesis has been reported in mice overexpressing CK2 and deficient in the
expression of p53. These and other data have indicated that the inappropriate expression of
CK2, in cooperation with other proteins, might augment the oncogenic potential of cells. In
line with these observations, the phosphatidylinositol 3-kinase (PI3K)/AKT signal
transduction pathway has also been shown to be central in many intracellular processes such
as proliferation, angiogenesis, motility and cell survival. The fact that a search for substrates
of AKT has led to the identification of several components of the apoptotic machinery, and
that the PI3K pathway is negatively regulated by PTEN, a dual-specificity lipid and protein
phosphatase considered to be a tumour suppressor gene product, gave, indeed, rise to the idea
that AKT is a key element in the regulation of cell survival. Recently, we were able to show
for the first time that the specific inhibition of the PI3K-AKT signaling pathway in
combination with the depletion of either CK2 subunits by antisense oligodeoxynucleotides
leads to an enhanced drug-induced apoptotic response. In vitro as well as in vivo studies have
revealed that the individual CK2 subunits interact with AKT enhancing AKT kinase activity
and that the complex formation is not modulated by the phosphorylation status of AKT. These
data 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. Moreover, they underline the importance of developing
efficient strategies to directly inhibit AKT and CK2 as valuable therapeutic approach in
cancer therapy.
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