Figure 3.

Mechanism of cell cycle progression mediated by E2F. In the resting state, the DREAM complex, including repressor E2Fs and p130, actively suppresses E2F target gene expression. Upon growth stimulation, the expression of cyclin D is induced, activating CDK4/6, which phosphorylates p130 and relieves repression by the DREAM complex. Repressor E2Fs, freed from repression by the DREAM complex, now induces the expression of growth-related genes such as cyclin E and activator E2Fs, further inactivating pRB and activating E2F. This feedback loop shifts RB inactivation and E2F activation from the growth-dependent D-type CDK to the E2F-dependent E-type CDK, thereby facilitating transit through the restriction point. After the restriction point, progression of the cell cycle proceeds autonomously to the end of mitosis.