title: Functional interaction of protein kinase CK2 and c-Myc in lymphomagenesis.
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.
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, MA 02118, USA.
authors.forename: Padmalatha
authors.initials: P
authors.lastname: Channavajhala
authors.forename: David C
authors.initials: DC
authors.lastname: Seldin
mesh_terms: D000818:Animals; D047310:Apigenin; D015153:Blotting, Western; D047390:Casein Kinase II; D002455:Cell Division; D002478:Cells, Cultured; D004642:Emodin / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D008223:Lymphoma / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010447:Peptide Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D010957:Plasmids; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D005419:Flavonoids; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D047310:Apigenin; D005982:Glutathione Transferase; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D010447:Peptide Hydrolases; D004642:Emodin