Building p53.

The intricacies of p53 regulation just got more complex. While much is known about the transcriptional regulation of p53 target genes, Chen and Kastan (pp. 2146-2156) uncovered a new mechanism regarding the making of the p53 protein itself. In the October 1, 2010, issue of Genes & Development, they introduced us to a novel mechanism of p53 translational control, by which a 5'-3' cap-independent, poly(A)-independent, RNA-RNA interaction enhances p53 translation by binding the ribosomal protein RPL26 following DNA damage. Oligonucleotides designed against this 5'-3' untranslated region (UTR) duplex disrupted the binding of RPL26 to p53 mRNA and reduced p53 synthesis and, therefore, function. This study reveals an alternate mechanism of translational control to regulate p53 levels.