human vrk1 is an early response gene and its loss causes a block in cell cycle progression人类vrk1是早期反应基因及其损失导致细胞周期进展一块.pdfVIP

Human VRK1 Is an Early Response Gene and Its Loss Causes a Block in Cell Cycle Progression ´ ´ Alberto Valbuena, Inmaculada Lopez-Sanchez, Pedro A. Lazo* ´ ´ ´ ´ ´ Programa de Oncologıa Translacional, Instituto de Biologıa Molecular y Celular del Cancer, Centro de Investigacion del Cancer (CIC), Consejo Superior de Investigaciones ´ Cientıficas (CSIC), Universidad de Salamanca, Salamanca, Spain Abstract Background: In mammalian cells regulatory proteins controlling the cell cycle are necessary due to the requirements of living in a heterogeneous environment of cell-interactions and growth factors. VRK1 is a novel serine-threonine kinase that phosphorylates several transcription factors and is associated with proliferation phenotypes. Methodology/Principal Findings: In this report VRK1 has been identified as regulated in the cell cycle. VRK1 gene expression is activated by the addition of serum to starved cells, indicating it is required for the exit of G0 phase and entry in G1; a response that parallels the re-expression of MYC, FOS and CCND1 (cyclin D1) genes, suggesting that VRK1 is an early- response gene. VRK1 gene expression is also shutdown by serum withdrawal. The human VRK1 gene promoter cloned in a luciferase reporter responds similarly to serum. In response to serum, the level of VRK1 protein expression has a positive correlation with cell proliferation markers such as phosphorylated-Rb or PCNA, and is inversely correlated with cell cycle inhibitors such as p27. The elimination of VRK1 by siRNA results in a G1 block in cell division, and in loss of phosphorylated- Rb, cyclin D1, and other proliferation markers. Elimination of VRK1