 Cyclin E/CDK2 also phosphorylates p27 and p21 during G1 and S phases, respectively.Smad3, a key mediator of TGF-β pathway which inhibits cell cycle progression, can be phosphorylated by cyclin E/CDK2.The phosphorylation of Smad3 by cyclin E/CDK2 inhibits its transcriptional activity and ultimately facilitates cell cycle progression.