TBBz but not TBBt discriminates between two molecular forms of CK2 in vivo and its implications

Biochem Biophys Res Commun. 2003 Dec 19;312(3):623-8. doi: 10.1016/j.bbrc.2003.10.165.

Abstract

Two ATP-competitive inhibitors-4,5,6,7-tetrabromo-benzotriazole (TBBt) and 4,5,6,7-tetrabromo-benzimidazole (TBBz) have been shown to decrease activity of CK2 holoenzyme. Surprisingly it occurs that TBBz contrary to TBBt does not inhibit free catalytic subunit CK2 [Formula: see text]. Both inhibitors are virtually inactive against RAP protein kinase. The above-mentioned protein kinases phosphorylate in vitro a set of acidic ribosomal P-proteins of the 60S ribosomal subunit. Such a modification is one of the mechanisms regulating translational activity of ribosomes in vivo. Application of these two very selective inhibitors allows us to define the role of free catalytic [Formula: see text] subunit of CK2 in phosphorylation of ribosomal proteins. It occurs that CK2 [Formula: see text] but not CK2 holoenzyme is responsible for phosphorylation of P-proteins in vivo. Moreover, elimination of both forms of protein kinase CK2 (hCK2 and CK2 [Formula: see text] ) activity in living cells led to dramatic loss of the translational activity of the ribosome.

Publication types

  • Comparative Study

MeSH terms

  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Benzimidazoles / toxicity
  • Binding, Competitive
  • Casein Kinase II
  • Cell Division / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Protein Biosynthesis / drug effects
  • Protein Biosynthesis / physiology
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protozoan Proteins*
  • Ribosomal Proteins / chemistry
  • Ribosomal Proteins / metabolism*
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / enzymology*
  • Structure-Activity Relationship
  • Triazoles / chemistry
  • Triazoles / pharmacology*
  • Triazoles / toxicity

Substances

  • 4,5,6,7-tetrabromobenzimidazole
  • 4,5,6,7-tetrabromobenzotriazole
  • Benzimidazoles
  • L12E protein, Trypanosoma cruzi
  • Protozoan Proteins
  • Ribosomal Proteins
  • Triazoles
  • Casein Kinase II
  • Protein-Serine-Threonine Kinases