Santos Claudio R, Rodríguez-Pinilla María, Vega Francisco M, Rodríguez-Peralto José L, Blanco Sandra, Sevilla Ana, Valbuena Alberto, Hernández Teresa, van Wijnen André J, Li Fengzhi, de Alava Enrique, Sánchez-Céspedes Montserrat, Lazo Pedro A
Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Cientificas, Universidad de Salamanca, Campus Miguel de Unamuno, E-37007 Salamanca, Spain.
Mol Cancer Res. 2006 Mar;4(3):177-85. doi: 10.1158/1541-7786.MCR-05-0212.
The vaccinia-related kinase (VRK) proteins are a new family with three members in the human kinome. The VRK1 protein phosphorylates several transcription factors and has been postulated to be involved in regulation of cell proliferation. In normal squamous epithelium, VRK1 is expressed in the proliferation area. Because VRK1 can stabilize p53, the expression of the VRK1 protein was analyzed in the context of the p53 pathway and the proliferation phenotype in a series of 73 head and neck squamous cell carcinomas. VRK1 protein level positively correlated with p53 response proteins, particularly hdm2 and p21. The VRK1 protein also correlated positively with several proteins associated with proliferation, such as cyclin-dependent kinase 2 (CDK2), CDK6, cdc2, cyclins B1 and A, topoisomerase II, survivin, and Ki67. The level of VRK1 protein behaves like a proliferation marker in this series of head and neck squamous cell carcinomas. To identify a possible regulatory role for VRK1 and because it regulates gene transcription, the promoters of two genes were studied, CDK2 and SURVIVIN, whose proteins correlated positively with VRK1. VRK1 increases the activity of both the CDK2 and SURVIVIN gene promoters. The expression of VRK1 was analyzed in the context of regulators of the G1-S transition. VRK1 protein levels increase in response to E2F1 and are reduced by retinoblastoma and p16. These data suggest that VRK1 might play a role in cell cycle regulation and is likely to represent the beginning of a new control mechanism of cell cycle, particularly late in the G1-S phase.
痘苗相关激酶（VRK）蛋白是人类激酶组中的一个新家族，有三个成员。VRK1蛋白可使多种转录因子磷酸化，并被推测参与细胞增殖的调控。在正常鳞状上皮中，VRK1在增殖区域表达。由于VRK1可稳定p53，因此在73例头颈部鳞状细胞癌系列研究中，结合p53信号通路和增殖表型对VRK1蛋白的表达进行了分析。VRK1蛋白水平与p53反应蛋白呈正相关，尤其是hdm2和p21。VRK1蛋白还与几种增殖相关蛋白呈正相关，如细胞周期蛋白依赖性激酶2（CDK2）、CDK6、cdc2、细胞周期蛋白B1和A、拓扑异构酶II、生存素和Ki67。在这一系列头颈部鳞状细胞癌中，VRK1蛋白水平表现得像一个增殖标志物。为了确定VRK1可能的调控作用，并且由于它调节基因转录，研究了两个基因CDK2和生存素的启动子，它们的蛋白与VRK1呈正相关。VRK1可增加CDK2和生存素基因启动子的活性。在G1-S期转换调节因子的背景下分析了VRK1的表达。VRK1蛋白水平对E2F1有反应而升高，而被视网膜母细胞瘤和p16降低。这些数据表明，VRK1可能在细胞周期调控中发挥作用，并且可能代表了一种新的细胞周期控制机制的开端, 尤其是在G1-S期晚期。
