Figure 4

Role of TGF-β in regulation of cell cycle. Physiologically, TGF-β is a potent inhibitor of cell cycle; it induces expression of p15^INK4B and represses expression of c-Myc. p15^INK4B is able to prevent cyclin D-CDK4/6 complex formation; moreover, it displaces p21^CIP1 and p27^KIP1 from cyclin D-CDK4/6 complexes. These CIP/KIP inhibitors are subsequently able to inactivate other complexes of G1 and S phase and thereby inhibit cell cycle. Moreover, low levels of c-Myc allows for TGF-β induced p15^INK4B and p21^CIP1 transcription