Module 9: Figure cyclin D/CDK action
Cyclin D/cyclin-dependent kinase 4/6 (CDK4/6) activation of cyclin E transcription.
The grey box at the bottom represents the repressed state of the cyclin E gene as occurs in G0 when cell proliferation is arrested. There are two promoter sites where the pocket proteins [retinoblastoma protein (Rb), p107 and p130] and the E2F proteins (Module 9: Figure Rb–E2F interactions) interact to repress gene transcription. At one site, the transcriptional activator E2F is repressed by the Rb, which also contributes to repression by binding the histone deacetylase (HDAC). At the other site, the pocket proteins p107 and p130 facilitate the binding of the E2F4/5 transcriptional repressors. When cells are stimulated to grow, there is an increase in the level of cyclin D that sets off a cascade of events that lead to activation of the cyclin E gene, as described in the text.