The novel PIAS-like protein hZimp10 is a transcriptional co-activator of the p53 tumor suppressor

Abstract

The tumor suppressor, p53, plays critical roles in the cell cycle progression, DNA repair and apoptosis. The PIAS proteins (protein inhibitor of activated STAT) were originally identified as inhibitors of the JAK-STAT pathway. Subsequently, crosstalk between the PIAS proteins and other signaling pathways has been shown to be involved in various cellular processes. Particularly, previous studies have demonstrated that PIAS proteins regulate p53-mediated transcription through sumoylation. hZimp10, also named zmiz1, is a novel PIAS-like protein and functions as a transcriptional co-activator. We recently identified p53 to be an hZimp10 interacting protein in the yeast two-hybrid screen. The interaction between p53 and hZimp10 was confirmed by GST pull-down and co-immunoprecipitation assays. Co-localization of p53 and hZimp10 proteins was also observed within cell nuclei by immunostaining. Moreover, we show that expression of exogenous hZimp10 enhances the transcriptional activity of p53 and knockdown of endogenous hZimp10 reduces the transcriptional activity of p53. Furthermore, using chromatin immunoprecipitation assays, we demonstrate that hZimp10 binds to p53 on the p21 promoter. Finally, p53-mediated transcription is significantly impaired in Zimp10 null embryonic fibroblasts. Taken together, these results provide the first line of evidence to demonstrate a role for Zimp10 in regulating p53 function.