Functional interaction of protein kinase CK2 and c-Myc in lymphomagenesis
P Channavajhala, DC Seldin - Oncogene, 2002 - nature.com
P Channavajhala, DC Seldin
Oncogene, 2002•nature.comProtein 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 …
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 …
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.
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