butyrolactone-i and thiazolyl-blue

Hepatitis C virus (HCV) core protein is a multifunctional protein that affects transcription and cell growth in vitro and in vivo. Here, we confirm the proliferative activities of core protein in liver and non-liver cells and delineate part of the mechanism whereby core protein promotes cell growth. We show that core protein suppresses the expression of tumor suppressor protein p53 and cyclin-dependent kinase (CDK) inhibitor p21 and enhances the activation of cyclin-dependent kinase 2 (CDK2), the phosphorylation of retinoblastoma (Rb), the activation of the transcription factor E2F-1, and the expression of E2F-1 and S phase kinase-interacting protein 2 (SKP2) genes. Pretreatment of core protein-expressing cells with the inhibitor of CDK2, Butyrolactone I, abolished the phosphorylation of Rb, the activation of E2F-1, and inhibited the expression of E2F-1 gene and cell growth induced. Consistent with these findings, we define a new signaling pathway whereby the HCV core protein mediates cell growth in infected cells.

Topics: 4-Butyrolactone; Blotting, Northern; Cell Cycle Proteins; Cell Line; Cell Line, Tumor; Cell Nucleus; Cell Proliferation; DNA-Binding Proteins; DNA, Complementary; E2F Transcription Factors; E2F1 Transcription Factor; Enzyme Inhibitors; HeLa Cells; Hepacivirus; Humans; Liver; Luciferases; Phosphorylation; Plasmids; Protein Kinase Inhibitors; Retinoblastoma Protein; RNA; Signal Transduction; Tetrazolium Salts; Thiazoles; Thymidine; Transcription Factors; Tumor Suppressor Protein p53