Cellular and Molecular Biochemistry Research Laboratory, Research Service, Minneapolis V.A. Medical Center, and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55417, USA.
Biofactors. 2010 May-Jun;36(3):187-95. doi: 10.1002/biof.96.
Protein kinase CK2, a protein serine/threonine kinase, plays a global role in activities related to cell growth, cell death, and cell survival. CK2 has a large number of potential substrates localized in diverse locations in the cell including, for example, NF-kappaB as an important downstream target of the kinase. In addition to its involvement in cell growth and proliferation it is also a potent suppressor of apoptosis, raising its key importance in cancer cell phenotype. CK2 interacts with diverse pathways which illustrates the breadth of its impact on the cellular machinery of both cell growth and cell death giving it the status of a "master regulator" in the cell. With respect to cancer, CK2 has been found to be dysregulated in all cancers examined demonstrating increased protein expression levels and nuclear localization in cancer cells compared with their normal counterparts. We originally proposed CK2 as a potentially important target for cancer therapy. Given the ubiquitous and essential for cell survival nature of the kinase, an important consideration would be to target it specifically in cancer cells while sparing normal cells. Towards that end, our design of a tenascin based sub-50 nm (i.e., less than 50 nm size) nanocapsule in which an anti-CK2 therapeutic agent can be packaged is highly promising because this formulation can specifically deliver the cargo intracellularly to the cancer cells in vivo. Thus, appropriate strategies to target CK2 especially by molecular approaches may lead to a highly feasible and effective approach to eradication of a given cancer.
蛋白激酶 CK2 是一种蛋白丝氨酸/苏氨酸激酶，在与细胞生长、细胞死亡和细胞存活相关的活动中发挥着全局作用。CK2 有大量的潜在底物定位于细胞的不同位置，例如 NF-κB，作为激酶的一个重要下游靶标。除了参与细胞生长和增殖外，它还是凋亡的有效抑制剂，这使其在癌细胞表型中具有关键的重要性。CK2 与多种途径相互作用，这说明了它对细胞生长和细胞死亡的细胞机制的广泛影响，使它成为细胞中的“主调控因子”。就癌症而言，已经发现 CK2 在所有检查的癌症中失调，与正常细胞相比，癌细胞中的蛋白表达水平和核定位增加。我们最初提出 CK2 是癌症治疗的一个潜在重要靶点。鉴于激酶对细胞生存的普遍和必需性，一个重要的考虑因素将是在癌细胞中特异性地靶向它，同时保留正常细胞。为此，我们设计了一种基于 tenascin 的亚 50nm（即小于 50nm 大小）纳米胶囊，其中可以包装一种抗 CK2 治疗剂，这是非常有前途的，因为这种制剂可以在体内将 cargo 特异性地递送到癌细胞内。因此，通过分子方法靶向 CK2 的适当策略，特别是通过分子方法靶向 CK2 的适当策略，可能会导致一种非常可行和有效的消除特定癌症的方法。
