CK2 kinase activity but not its binding to CK2 promoter regions is implicated in the regulation of CK2α and CK2β gene expressions

Mol Cell Biochem. 2013 Dec;384(1-2):71-82. doi: 10.1007/s11010-013-1782-8. Epub 2013 Aug 21.

Abstract

Protein kinase CK2, a ubiquitous serine/threonine kinase in control of a variety of crucial cellular functions, is composed of catalytic α- and α'-subunits and non-catalytic β-subunits which form holoenzymes such as CK2(αβ)2, CK2αα'β2, or CK2(α'β)2. In addition, there is ample evidence for the occurrence of the individual subunits beside the holoenzyme. While the CK2 subunits are well analyzed on the protein level, only little is known about the regulation of their transcription. The existence of multiple forms of CK2 subunits raised the question about a mutual regulation of their expression. Here we defined two 5'-upstream regions of the CK2α and the CK2β genes, respectively, as sequences with promoter activities. We found that CK2α and CK2α' stimulated the expression of the reporter constructs whereas, CK2β was inactive. Using chromatin immunoprecipitation assays, we were unable to detect binding of endogenous CK2 subunits to these promoter sequences in vivo. However, it turned out that inhibition of the kinase activity of CK2 attenuated the promoter activity indicating that CK2α and CK2α' might regulate their gene expression indirectly by phosphorylation reactions. Thus, we have shown here (i) that under normal physiological conditions CK2 does not bind to CK2 promoter regions and (ii) that the CK2 kinase activity is implicated in the regulation of its own expression.

MeSH terms

  • Casein Kinase II / genetics*
  • Casein Kinase II / metabolism*
  • Catalytic Domain / genetics
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression
  • Gene Expression Regulation / genetics*
  • HCT116 Cells
  • Humans
  • Phosphorylation
  • Promoter Regions, Genetic / genetics*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism

Substances

  • DNA-Binding Proteins
  • Protein Isoforms
  • Casein Kinase II