Inhibition of cyclin D-CDK4/CDK6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity.

摘要: Alterations of various components the cell cycle regulatory machinery that controls progression cells from a quiescent to growing state contribute development many human cancers. Such alterations include deregulated expression G1 cyclins, loss function activities such as those protein p16INK4a control cyclin-dependent kinase activity, and retinoblastoma (RB), which is normally regulated by kinases. Various studies have revealed an inverse relationship in presence functional RB lines. In this study we show expressed cervical cancer lines gene, Rb, not functional, either consequence Rb mutation or papillomavirus E7 protein. We also demonstrate levels are increased primary has been inactivated DNA tumor virus proteins. Given role controlling E2F transcription factor investigated expression. found E2F1 overexpression leads inhibition cyclin D1-dependent activity induces p16-related transcript. conclude accumulation during normal through inactivation RB, then induction inhibitor shutdown activity.