Functional interaction of protein kinase CK2 and c-Myc in lymphomagenesis.
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.
Channavajhala
Padmalatha
P
Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, MA 02118, USA.
Seldin
David C
DC
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
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