Mitotic G1 phase and G1/S transition

During early G1, cells can enter a quiescent G0 state. In quiescent cells, the evolutionarily conserved DREAM complex, consisting of the pocket protein family member p130 (RBL2), bound to E2F4 or E2F5, and the MuvB complex, represses transcription of cell cycle genes (reviewed by Sadasivam and DeCaprio 2013).

During early G1 phase in actively cycling cells, transcription of cell cycle genes is repressed by another pocket protein family member, p107 (RBL1), which forms a complex with E2F4. RB1 tumor suppressor, the product of the retinoblastoma susceptibility gene, is the third member of the pocket protein family. RB1 binds to E2F transcription factors E2F1, E2F2 and E2F3 and inhibits their transcriptional activity, resulting in prevention of G1/S transition. Once RB1 is phosphorylated on serine residue S795 by Cyclin D:CDK4/6 complexes, it can no longer associate with and inhibit E2F1-3. Thus, CDK4/6-mediated phosphorylation of RB1 leads to transcriptional activation of E2F1-3 target genes needed for the S phase of the cell cycle. CDK2, in complex with cyclin E, contributes to RB1 inactivation and also activates proteins needed for the initiation of DNA replication. Expression of D type cyclins is regulated by extracellular mitogens. Catalytic activities of CDK4/6 and CDK2 are controlled by CDK inhibitors of the INK4 family and the Cip/Kip family, respectively.