p53 binds selectively to the 5 ' untranslated region of cdk4, an RNA element necessary and sufficient for transforming growth factor beta- and p53-mediated translational inhibition of cdk4

One consequence of transforming growth factor beta (TGF-beta) treatment is inhibition of Cdk4 synthesis, and this is dependent on p53. Here, we show t hat the 5' untranslated region (UTR) of the cdk4 mRNA is both necessary and sufficient for wild-type p53-dependent TGF-beta -regulated translational i nhibition of cdk4. Wild-type p53 bound selectively to the 5' UTR of the cdk 4 mRNA and inhibited translation of RNAs that contain this region. RNA bind ing and translational control are two genetically separable functions of p5 3, as are specific and nonspecific RNA binding. Moreover, transactivation-d efective mutants of p53 retain the ability to regulate cdk4 translation. Ou r findings suggest that p53 functions as a regulator of translation in resp onse to TGF-beta in vivo.