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Fig. 5. Epithelial growth suppression induced by TGF-ß. The TGF-ß receptors activate Smads, which induce p21 expression in cooperation with the transcription factors FoxO, p53 and Sp1. The Smad pathway also induces transcription of p15 or p57 and represses expression of Myc and Id genes. The net result of all these transcriptional events is the arrest of the cell cycle in early G1 phase. Smads can also activate PKA, which leads to Sp1 phosphorylation and induction of p21 expression. The TGF-ß receptor also binds the regulatory subunit Ba of PP2A phosphatase, leading to inactivation of p70 S6K kinase, thus indirectly inhibiting cell-cycle progression.





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