Functional interaction of protein kinase CK2 and c-Myc in lymphomagenesis

Oncogene. 2002 Aug 8;21(34):5280-8. doi: 10.1038/sj.onc.1205640.

Abstract

Protein kinase CK2 (formerly casein kinase II) is frequently upregulated in human cancers, and transgenic expression of CK2alpha in lymphocytes is oncogenic. Lymphomagenesis is dramatically accelerated by co-expression of a c-myc transgene, suggestive of a synergistic interaction between the kinase and the transcription factor. Since c-myc can be phosphorylated by CK2, we hypothesized that the synergy between CK2 and c-myc might be due to a functional interaction of the two molecules. Pharmacologic inhibition of CK2 activity in cell lines established from CK2alpha transgenic T cell lymphomas reduces their proliferation and concomitantly with this, the steady state levels of c-myc protein decline. This is caused by accelerated c-myc protein turnover, which occurs in a proteasome-dependent manner. Transfection of cells with sense or anti-sense CK2 constructs modulates c-myc protein levels in concert with the alteration in CK2 activity, validating the findings obtained using the kinase inhibitors. Thus, CK2 is a critical regulator of c-myc protein stability and of the proliferation of these T cell lymphomas.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apigenin
  • Blotting, Western
  • Casein Kinase II
  • Cell Division
  • Cells, Cultured
  • Emodin / pharmacology
  • Flavonoids / pharmacology
  • Glutathione Transferase / metabolism
  • Lymphoma / metabolism*
  • Mice
  • Mice, Transgenic
  • Peptide Hydrolases / metabolism
  • Phosphorylation
  • Plasmids
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • T-Lymphocytes / metabolism

Substances

  • Flavonoids
  • Proto-Oncogene Proteins c-myc
  • Recombinant Fusion Proteins
  • Apigenin
  • Glutathione Transferase
  • Casein Kinase II
  • Protein-Serine-Threonine Kinases
  • Peptide Hydrolases
  • Emodin