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  • Title: p53-dependent repression of CDK4 translation in TGF-beta-induced G1 cell-cycle arrest.
    Author: Ewen ME, Oliver CJ, Sluss HK, Miller SJ, Peeper DS.
    Journal: Genes Dev; 1995 Jan 15; 9(2):204-17. PubMed ID: 7851794.
    Abstract:
    Transforming growth factor beta 1 (TGF-beta 1) 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-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 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-beta 1 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.
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