Retinoblastoma (Rb) and p53 genes are mutated or inactivated in most human cancers and mutually regulate each other. Recently, we reported that expression of diverse genes was altered in Rb-deficient mouse embryonic fibroblasts (MEF). In this study, we found that Pierce1, a novel transcript upregulated in Rb-deficient MEFs, is a transcriptional target of p53. Although Pierce1 promoter did not respond to the ectopic expression of E2F1, it was strongly activated by p53 via 2 cis-elements. Consistently, the expression of Pierce1 was induced by genotoxic stresses that activate p53 but was not detected in p53-deficient MEFs. Pierce1 was posttranslationally stabilized by ultraviolet C (UVC) irradiation, and UVC-activated ATR (ataxia telangiectasia-mutated and Rad3-related) signaling suppressed proteosomal degradation of Pierce1 protein. Furthermore, knockdown of Pierce1 compromised the checkpoint response of wild-type MEFs to UVC irradiation, accompanying the diminished expression of p53 target genes. Together, our data suggest that Pierce1 is an important p53 target gene contributing to normal DNA damage response and may play crucial roles in maintaining genomic integrity against genotoxic stresses, including UVC irradiation.
All Science Journal Classification (ASJC) codes
- Cancer Research