IN VIVO MODULATION OF PROTEIN KINASE CK2 BY POLYAMINES

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Both polyamines and the serine/threonine protein kinase CK2 are required for cell proliferation and are elevated in solid tumors. Ornithine decarboxylase (ODC) is a key regulatory enzyme in the biosynthesis of polyamines. Accumulating evidence has demonstrated that increased levels of ODC and polyamines play an important role in tumor development. Our preliminary data suggest that a biological effect of ODC overexpression in cells is an increase in the kinase activity and the nuclear translocation of CK2. The overall goal of this project is to test the hypothesis that CK2 functions as a downstream effector of polyamines and that these polyamine-mediated modulations of CK2 activity and its subcellular localization account for some of the phenotypic changes seen in ODC overexpressing cells. Thus, we propose the following specific aims: 1. To determine the cell cycle dependent effects of increased levels of polyamines on CK2 expression and its subcellular localization. 2. To evaluate the effects of altering the interaction between polyamines and CK2 on: a) CK2 enzyme activity and substrate phosphorylation b) CK2 subcellular localization c) tumorigenicity. 3. To determine the effect of increased levels of polyamines on the phosphorylation status of known and novel substrates of CK2.