IN VIVO MODULATION OF PROTEIN KINASE CK2 BY POLYAMINES

需要多胺和丝氨酸/苏氨酸蛋白激酶CK 2 在实体瘤中升高。鸟氨酸 脱羧酶（ODC）是生物合成中的关键调节酶， 多胺 越来越多的证据表明， ODC和多胺水平在肿瘤发生发展中起重要作用 发展 我们的初步数据表明， ODC在细胞中的过表达是激酶活性的增加， CK 2的核转位。 该项目的总体目标是 为了验证CK 2作为下游效应子的假设， 这些多胺介导的CK 2活性调节 它的亚细胞定位解释了一些表型 在ODC过表达细胞中观察到的变化。 因此，我们建议 具体目标：1。 为了确定细胞周期依赖性 多胺水平升高对CK 2表达的影响及其 亚细胞定位。 2. 为了评估改变 多胺和CK 2之间的相互作用：a）CK 2酶活性和 底物磷酸化B）CK 2亚细胞定位c） 致瘤性 3. 为了确定增加水平的 多胺对已知和新底物磷酸化状态的影响 CK 2的。

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.