What regulates cell proliferation?

Cell proliferation is typically regulated during the first gap phase (G1) of the cell division cycle. Several signals ranging from growth factors to DNA damage to developmental signals control the decision to enter the S phase during DNA replication. More specifically, the process is highly regulated through the phosphorylation of cyclins and sometimes by proteins which target cyclins to E3 ubiquitin ligases. These ligases provide mechanisms for extracellular growth factors to cue to the G1 phase. Cell proliferation can also be regulated by signals that inhibit cell cycle progression. For example, substances that cause DNA damage may pause the cell cycle and allow time for DNA repair.