Polycomb Group Protein PHF1Regulates P53-dependent Cell Proliferation And Apoptosis

The p53tumor suppressor is critical for maintenance of genome stability and protection against malignant transformation. Polycomb group protein PHF1is well known as a component of a novel EED-EZH2/PRC2complex and plays important role in H3K27methylation and Hox gene silencing. PHF1was also involved in the response to DNA double-strand breaks in human cell, promotes nonhomologous end-joining processes through interaction with Ku70/Ku80. Here, we identified another function of PHF1as a potential p53pathway activator in a pathway screen using luminescence reporter assay. Subsequent studies showed PHF1directly interacts with p53proteins both in vivo and in vitro and co-localized in nucleus. PHF1binds to the C-terminal regulatory domain of p53. Overexpression of PHF1elevates p53protein level and prolongs its turnover. Knockdown of PHF1reduced p53protein level and target gene expression both in normal state and DNA damage response. Mechanically, PHF1protects p53proteins form Mdm2-meidated ubiquitination and degradation. Furthermore, we showed PHF1suppresses cell proliferation and etoposide-induced apoptosis in a p53-dependent manner. Taking together, we established PHF1as a novel positive regulator of p53pathway. These data shed light on the potential roles of PHF1in tumorigenesis and/or tumor progression.