The p15(PAF)/KIAA0101 protein is a proliferating cell nuclear antigen (PCNA)-associated protein overexpressed in multiple types of cancer.Attenuation of p15(PAF) expression leads to modifications in the DNA repair process, rendering cells more sensitive to ultraviolet-induced cell death.In this study, we identified that p15(PAF) expression peaks during the 730 sunken lake road S phase of the cell cycle.
We observed that p15(PAF) knockdown markedly inhibited cell proliferation, S-phase progression, and DNA synthesis.Depletion of p15(PAF) resulted in p21 upregulation, especially chromatin-bound p21.We weboost splitter further identified that the p15(PAF) promoter contains 3 E2F-binding motifs.
Loss of Rb-mediated transcriptional repression resulted in upregulated p15(PAF) expression.Binding of E2F4 and E2F6 to the p15(PAF) promoter caused transcriptional repression.Overall, these results indicate that p15(PAF) is tightly regulated by the Rb/E2F complex.
Loss of Rb/E2F-mediated repression during the G1/S transition phase leads to p15(PAF) upregulation, which facilitates DNA synthesis and S-phase progression.