International Journal of Molecular Sciences, Vol.15, No.2, 2573-2584, 2014
The Proteasome Activator PA28 gamma, a Negative Regulator of p53, Is Transcriptionally Up- Regulated by p53
PA28 (also called REG, 11S or PSME3) negatively regulates p53 activity by promoting its nuclear export and/or degradation. Here, using the RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE) method, we identified the transcription start site of the PA28 gene. Assessment with the luciferase assay demonstrated that the sequence -193 to +16 is the basal promoter. Three p53 binding sites were found within the PA28 promoter utilizing a bioinformatics approach and were confirmed by chromatin immunoprecipitation and biotinylated DNA affinity precipitation experiments. The p53 protein promotes PA28 transcription, and p53-stimulated transcription of PA28 can be inhibited by PA28 itself. Our results suggest that PA28 and p53 form a negative feedback loop, which maintains the balance of p53 and PA28 in cells.