p53 and translational control.
The tumor suppressor p53 plays a role in mediating a G1 arrest (for example, in response to DNA damage), in the cellular commitment to apoptosis 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 transcriptional activator. p53 can also repress transcription from certain promoters. One way in which p53 mediates a G1 arrest after DNA damage appears to be clear. Cells exposed to ionizing radiation show elevated levels of p53 protein. The increase in p53 levels is thought to be responsible for the increase in the cyclin-dependent kinase (cdk) inhibitor p21 mediated through the p53 binding sites in the p21 promoter. With regard to the ability of p53 to suppress transformation, there is data suggesting that p53 functions other than, or in addition to, its transcriptional activation function may be necessary. Similar data exist for p53-dependent apoptosis. Recently a role for p53 at another level of gene regulation, namely, translational regulation has been proposed. p53 associates with various components of the translation machinery and has been implicated in the translational regulation of both the p53 and CDK4 mRNAs. Here we will summarize the evidence suggesting a role for p53 in translation and how this regulation might be achieved.
Ewen
M E
ME
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Miller
S J
SJ
D005786:Gene Expression Regulation; D016158:Genes, p53; D006801:Humans; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53