title: p15(PAF) is an Rb/E2F-regulated S-phase protein essential for DNA synthesis and cell cycle progression.
abstract: 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 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 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.
authors.affiliation: Graduate Institute of Pathology, National Taiwan University, Taipei, Taiwan.
authors.forename: Chih-Ning
authors.initials: CN
authors.lastname: Chang
authors.forename: Mow-Jung
authors.initials: MJ
authors.lastname: Feng
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Chen
authors.forename: Ray-Hwang
authors.initials: RH
authors.lastname: Yuan
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D059372:Nucleotide Motifs; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D016196:S Phase / Q000235:genetics; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; C425208:PCLAF protein, human; D016160:Retinoblastoma Protein