Detailed studies on p53-regulated Wip1 expression revealed that p53 also regulates Wip1 expression through post-transcriptional control (Figure 3). Rossi et al. identified two clusters of PPM1D transcription start sites, distinguished by their 5′UTR lengths (19). The longer 5′UTR transcripts had about 220 bases of highly structured mRNA preceding the translation initiation codon, whereas the shorter 5′UTR transcripts had about 65 bases before the translation initiation codon. The authors showed that CREB binding to the CRE site was associated with production of transcripts with longer 5′UTRs. However, in response to UV radiation or IR, p53 bound to the p53RE enhanced transcription of Wip1 transcripts with shorter 5′UTRs. In fact, RT-PCR-based analysis with specific primers showed that the majority of the PPM1D transcripts induced by either UV radiation or IR exposure were the shorter species. Since shorter transcripts may be more efficiently exported from the nucleus, this represents a post-transcriptional mechanism through which p53 enhances Wip1 expression (19).
