CDK3 belongs to the cyclin-dependent protein kinase family and is a major player driving retinoblastoma (Rb) phosphorylation during the G0/G1 transition and in the early G1 phase of the cell cycle. CDK3 can also directly regulate the activity of E2 factor (E2F) by skipping the role of Rb in late G1, potentially via the phosphorylation of the E2F1 partner DP1. Beyond the cell cycle, CDK3 interacts with various transcription factors involved in cell proliferation, differentiation, and transformation driven by the epidermal growth factor receptor (EGFR)/rat sarcoma virus (Ras) signaling pathway.