p15PAF Is an Rb/E2F-Regulated S-Phase Protein Essential for DNA Synthesis and Cell Cycle Progression
Journal
PLoS ONE
Journal Volume
8
Journal Issue
4
Pages
e61196
Date Issued
2013
Author(s)
Abstract
The p15PAF/KIAA0101 protein is a proliferating cell nuclear antigen (PCNA)-associated protein overexpressed in multiple types of cancer. Attenuation of p15PAF expression leads to modifications in the DNA repair process, rendering cells more sensitive to ultraviolet-induced cell death. In this study, we identified that p15PAF expression peaks during the S phase of the cell cycle. We observed that p15PAF knockdown markedly inhibited cell proliferation, S-phase progression, and DNA synthesis. Depletion of p15PAF resulted in p21 upregulation, especially chromatin-bound p21. We further identified that the p15PAF promoter contains 3 E2F-binding motifs. Loss of Rb-mediated transcriptional repression resulted in upregulated p15PAF expression. Binding of E2F4 and E2F6 to the p15PAF promoter caused transcriptional repression. Overall, these results indicate that p15PAF is tightly regulated by the Rb/E2F complex. Loss of Rb/E2F-mediated repression during the G1/S transition phase leads to p15PAF upregulation, which facilitates DNA synthesis and S-phase progression. ? 2013 Chang et al.
SDGs
Other Subjects
nuclear protein; protein p15 PAF; protein p21; retinoblastoma protein; transcription factor E2F; transcription factor E2F4; transcription factor E2F6; unclassified drug; adult; article; cell cycle progression; cell cycle S phase; cell proliferation; controlled study; DNA synthesis; human; human cell; human tissue; promoter region; protein binding; protein expression; protein function; protein motif; transcription regulation; upregulation; Base Sequence; Binding Sites; Carrier Proteins; Cell Cycle; Cell Line; Chromatin; DNA Replication; E2F Transcription Factors; Gene Expression; Gene Knockdown Techniques; Humans; Nucleotide Motifs; Promoter Regions, Genetic; Protein Binding; Retinoblastoma Protein; S Phase; Signal Transduction
Type
journal article