title: Characterization of ATM and DNA-PK wild-type and mutant cell lines upon             DSB induction in the presence and absence of CK2 inhibitors.
abstract: 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.
authors: Institute for Biochemistry and Molecular Biology, University                     of Southern Denmark, 5230 Odense, Denmark.
authors: Birgitte B
authors: BB
authors: Olsen
authors: Gerhard
authors: G
authors: Fritz
authors: Olaf-Georg
authors: OG
authors: Issinger
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded; D051747:DNA-Activated Protein Kinase / Q000172:deficiency / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D055786:Gene Knockout Techniques; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism*; D010078:Oxazines / Q000494:pharmacology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D009353:Zinostatin
chemical_list: C492322:2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole; D051023:BH3 Interacting Domain Death Agonist Protein; D001562:Benzimidazoles; C494815:Bid protein, mouse; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010078:Oxazines; D025521:Tumor Suppressor Proteins; C014180:resorufin; D009353:Zinostatin; C514862:Akt1 protein, mouse; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D047390:Casein Kinase II; D051747:DNA-Activated Protein Kinase; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C497264:Prkdc protein, mouse; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3