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The role of TGF-β in cell cycle regulation. Physiologically, TGF-β is a potent cell cycle inhibitor, inducing the expression of p15INK4B and suppressing c-Myc expression. p15INK4B prevents the formation of cyclin D-CDK4/6 complexes and displaces p21Cip1 and p27KIP1 from the cyclin D-CDK4/6 complex. The inhibitors CIP/KIP can then inactivate other G1 to S phase complexes and inhibit the cell cycle. Low c-Myc levels allow TGF-β to induce the transcription of p15INK4B and p21Cip21.
