Requirement of Casein Kinase 2 for Entry Into and Progression Through Early Phases of the Cell Cycle

Cell Mol Biol Res. 1994;40(5-6):519-27.

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)

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Base Sequence
  • Casein Kinase II
  • Cell Cycle*
  • Fibroblasts
  • G1 Phase
  • Humans
  • Lung
  • Microinjections
  • Molecular Sequence Data
  • Oligonucleotides, Antisense / pharmacology
  • Protein Conformation
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / genetics
  • Resting Phase, Cell Cycle
  • Signal Transduction

Substances

  • Antibodies, Monoclonal
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Casein Kinase II
  • Protein-Serine-Threonine Kinases