p53-dependent repression of CDK4 translation in TGF-β-induced G1 cell-cycle arrest

Abstract

Transforming growth factor β1 (TGF-β1) can cause a cell-cycle arrest in G1. Inhibition of cyclin-dependent kinase 4 (cdk4) synthesis plays a significant role in the mechanism by which this cytokine causes G1 growth arrest. Deregulated expression of cdk4 confers resistance to TGF-β1. Here, we show that TGF-β1 down-regulates cdk4 expression by inhibiting its translation. Moreover, mutant p53 confers resistance to TGF-β1 by interfering with the down-regulation of cdk4 in response to the cytokine. In contrast, we demonstrate that wild-type p53 represses the translation of CDK4. Regulation of cdk4 synthesis by both p53 and TGF-β1 is mediated by the 5′-untranslated region of the CDK4 message. Thus, regulation of CDK4 translation may be involved in control of G1 progression by p53.