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 CK2α in lymphocytes is oncogenic. Lymphomagenesis is dramatically acclerated by co-expression of a c-myctransgene, suggestive of a synergistic interaction between the kinase and the transcription factor. Since c-myccan be phosphorylated by CK2, we hypothesized that the synergy between CK2 and c-mycmight be due to a functional interaction of the two molecules. Pharmacologic inhibition of CK2 activity in cell lines established from CK2α transgenic T cell lymphomas reduces their proliferation and concomitantly with this, the steady state levels of c-mycprotein decline. This is caused by acclerated c-mycprotein turnover, which occurs in a proteasome-dependent manner. Transfection of cells with sense or anti-sense CK2 constructs modulates c-mycprotein 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-mycprotein stability and of the proliferation of these T cell lymphomas.