Schwind Lisa, Schetting Sarah, Montenarh Mathias
Medical Biochemistry and Molecular Biology, Saarland University, Building 44, D-66424 Homburg, Germany.
Pharmaceuticals (Basel). 2017 Feb 9;10(1):22. doi: 10.3390/ph10010022.
Protein kinase CK2 as a holoenzyme is composed of two catalytic α- or α'-subunits and two non-catalytic β-subunits. Knock-out experiments revealed that CK2α and CK2β are required for embryonic development. Little is known about the role of CK2 during differentiation of stem cells. Mesenchymal stem cells (MSCs) are multipotent cells which can be differentiated into adipocytes in vitro. Thus, MSCs and in particular C3H/10T1/2 cells are excellent tools to study a possible role of CK2 in adipogenesis. We found downregulation of the CK2 catalytic subunits as well as a decrease in CK2 kinase activity with progression of differentiation. Inhibition of CK2 using the potent inhibitor CX-4945 impeded differentiation of C3H/10T1/2 cells into adipocytes. The inhibited cells lacked the observed decrease in CK2 expression, but showed a constant expression of all three CK2 subunits. Furthermore, inhibition of CK2 resulted in decreased cell proliferation in the early differentiation phase. Analysis of the main signaling cascade revealed an elevated expression of C/EBPβ and C/EBPδ and reduced expression of the adipogenic master regulators C/EBPα and PPARγ2. Thus, CK2 seems to be implicated in the regulation of different steps early in the adipogenic differentiation of MSC.
蛋白激酶CK2作为一种全酶，由两个催化性α-或α'-亚基和两个非催化性β-亚基组成。基因敲除实验表明，胚胎发育需要CK2α和CK2β。关于CK2在干细胞分化过程中的作用知之甚少。间充质干细胞（MSC）是多能细胞，可在体外分化为脂肪细胞。因此，MSC尤其是C3H/10T1/2细胞是研究CK2在脂肪生成中可能作用的优秀工具。我们发现随着分化进程，CK2催化亚基下调以及CK2激酶活性降低。使用强效抑制剂CX-4945抑制CK2会阻碍C3H/10T1/2细胞向脂肪细胞的分化。被抑制的细胞没有出现观察到的CK2表达下降，但所有三个CK2亚基都呈现恒定表达。此外，抑制CK2会导致早期分化阶段细胞增殖减少。对主要信号级联的分析显示，C/EBPβ和C/EBPδ表达升高，而成脂主调节因子C/EBPα和PPARγ2表达降低。因此，CK2似乎参与了MSC成脂分化早期不同步骤的调控。
