Transforming growth factor beta 1 (TGF-beta 1) can cause a cell-cycle
arrest in G(1). Inhibition of cyclin-dependent kinase 4 (cdk4) synthes
is plays a significant role in the mechanism by which this cytokine ca
uses G(1) growth arrest. Deregulated expression of cdk4 confers resist
ance to TGF-beta 1. Here, we show that TGF-beta 1 down regulates cdk4
expression by inhibiting its translation. Moreover, mutant p53 confers
resistance to TGF-beta 1 by interfering with the down-regulation of c
dk4 in response to the cytokine. In contrast, we demonstrate that wild
-type p53 represses the translation of CDK4. Regulation of cdk4 synthe
sis by both p53 and TGF-beta 1 is mediated by the 5'-untranslated regi
on of the CDK4 message. Thus, regulation of CDK4 translation may be in
volved in control of G(1) progression by p53.