title: Requirement of casein kinase 2 for entry into and progression through early phases of the cell cycle.
abstract: Requirement of protein kinase CK2 during cell cycle was examined by specific perturbation of CK2 in the intact cell by antisense-oligodeoxynucleotides and microinjection of antibodies. When quiescent human primary lung fibroblasts (IMR-90) were exposed before growth stimulation to oligodeoxynucleotides complementary to the translation start region of mRNAs encoding subunit alpha or beta, a significant inhibition of growth stimulation by epidermal growth factor or serum was observed. The inhibition was reversible and decreased or abolished with mutated antisense-oligodeoxynucleotides. The inhibitory effect coincided with a decrease of CK2 protein (immunostaining with beta subunit antibody) at entry into and during the first several hours of the cell cycle. Injection of beta-specific monoclonal and polyclonal antibodies into IMR-90 cells caused significant inhibition of growth stimulation. The inhibition was reversible, not observed with control antibodies, and strongly reduced by coinjection of CK2 holoenzyme. Cytoplasmic injection inhibited up to 50-60% and was effective at two intervals within the first 2 h and at 12-16 h poststimulation, i.e., at G0/G1 phase transition and at G1/S boundary, respectively. The inhibition at G0/G1 transition is paralleled by an inhibition of cytoplasmic-nuclear translocation of beta subunit protein. Injection of beta antibodies into the nucleus inhibited growth stimulation by as much as 80-85% and was effective for the first 6 h poststimulation, i.e., at G0/G1 phase transition and progression through the adjoining early G1 phase. Nuclear as well as cytoplasmic injections performed during S phase affected neither DNA synthesis nor cell division.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Lorenz
authors.forename: R
authors.initials: R
authors.lastname: Pepperkok
authors.forename: W
authors.initials: W
authors.lastname: Pyerin
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D047390:Casein Kinase II; D002453:Cell Cycle; D005347:Fibroblasts; D016193:G1 Phase; D006801:Humans; D008168:Lung; D008845:Microinjections; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics; D016192:Resting Phase, Cell Cycle; D015398:Signal Transduction
chemical_list: D000911:Antibodies, Monoclonal; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases