P53 AND TRANSLATIONAL CONTROL

The tumor suppressor p53 plays a role in mediating a G1 arrest (for ex ample, in response to DNA damage), in the cellular commitment to apopt osis and in suppression of transformation. The mechanism of action of p53 in each of these biological outcomes is likely to be overlapping. Current data indicate that p53 functions as a sequence specific transc riptional activator. p53 can also repress transcription from certain p romoters. One way in which p53 mediates a G1 arrest after DNA damage a ppears to be clear. Cells exposed to ionizing radiation show elevated levels of p53 protein. The increase in p53 levels is thought to be res ponsible for the increase in the cyclin-dependent kinase (cdk) inhibit or p21 mediated through the p53 binding sites in the p21 promoter. Wit h regard to the ability of p53 to suppress transformation, there is da ta suggesting that p53 functions other than, or in addition to, its tr anscriptional activation function may be necessary [1,2]. Similar data exist for p53-dependent apoptosis [3-5]. Recently a role for p53 at a nother level of gene regulation, namely, translational regulation has been proposed. p53 associates with various components of the translati on machinery and has been implicated in the translational regulation o f both the p53 and CDK4 mRNAs. Here we will summarize the evidence sug gesting a role for p53 in translation and how this regulation might be achieved.