zinostatin and resorufin

Protein kinase CK2 is involved in several cellular processes and has lately also been linked to the DNA damage response through phosphorylations and interactions. Herein, we have analysed two sets of mouse cell lines, one pair, which is proficient and deficient in ATM and the other set expressing or lacking a functional catalytic subunit of the DNA dependent protein kinase (DNA-PKcs). Both kinases are implicated in the downstream phosphorylation of the signaling molecules such as BID and AKT1 in response to DNA damage. BID and AKT1 are also targets of CK2, hence the four cell lines were treated with the three established CK2 inhibitors DMAT, TBB and resorufin in the absence and presence of the radiomimetic drug neocarzinostatin, which induces DNA double-strand breaks. We show that there are differences with respect to the effect of the CK2 inhibitors on the phosphorylation of AKT1 at S473 and its downstream target GSK3β as well as between the two sets of cell lines. However, no such change was seen with BID phosphorylation. The most notably difference was the higher expression of CK2α' and CK2β in DNA-PKcs defective cells compared to the DNA-PKcs proficient cells.

Topics: Animals; Ataxia Telangiectasia Mutated Proteins; Benzimidazoles; BH3 Interacting Domain Death Agonist Protein; Casein Kinase II; Cell Cycle Proteins; Cells, Cultured; DNA Breaks, Double-Stranded; DNA-Activated Protein Kinase; DNA-Binding Proteins; Fibroblasts; Gene Knockout Techniques; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Mice; Mice, Inbred BALB C; Mice, SCID; Nuclear Proteins; Oxazines; Phosphorylation; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Tumor Suppressor Proteins; Zinostatin