The study investigates the mechanism by which transforming growth factor β (TGF-β) induces the cyclin-dependent kinase inhibitor p21 through a p53-independent pathway. TGF-β is known to inhibit cell cycle progression by regulating G1 cyclins and their kinase partners. The authors found that TGF-β rapidly induces p21 transcription, leading to increased association of p21 with cyclin D1 and Cdk2, which results in decreased Cdk2 kinase activity. This induction of p21 is not dependent on wild-type p53, as demonstrated by the inability of two mutant p53 alleles in the HaCaT cell line to activate the p21 promoter. The study also shows that the regions of the p21 promoter responsible for TGF-β-induced activation are distinct from those activated by p53. These findings suggest that TGF-β can induce p21 through multiple signaling pathways, highlighting the complexity of TGF-β-mediated growth inhibition.The study investigates the mechanism by which transforming growth factor β (TGF-β) induces the cyclin-dependent kinase inhibitor p21 through a p53-independent pathway. TGF-β is known to inhibit cell cycle progression by regulating G1 cyclins and their kinase partners. The authors found that TGF-β rapidly induces p21 transcription, leading to increased association of p21 with cyclin D1 and Cdk2, which results in decreased Cdk2 kinase activity. This induction of p21 is not dependent on wild-type p53, as demonstrated by the inability of two mutant p53 alleles in the HaCaT cell line to activate the p21 promoter. The study also shows that the regions of the p21 promoter responsible for TGF-β-induced activation are distinct from those activated by p53. These findings suggest that TGF-β can induce p21 through multiple signaling pathways, highlighting the complexity of TGF-β-mediated growth inhibition.