p15(PAF) is an Rb/E2F-regulated S-phase protein essential for DNA synthesis and cell cycle progression
| Autor: | Yu-Ling Chen, Mow-Jung Feng, Ray-Hwang Yuan, Chih-Ning Chang, Yung-Ming Jeng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Ophthalmologic Tumors
Gene Expression lcsh:Medicine Retinoblastoma Protein S Phase Molecular cell biology Promoter Regions Genetic lcsh:Science Multidisciplinary Cell Cycle Retinoblastoma Retinoblastoma protein Cell cycle respiratory system Chromatin Cell biology Nucleic acids DNA-Binding Proteins Oncology Gene Knockdown Techniques Medicine lipids (amino acids peptides and proteins) Cell Division Research Article Protein Binding Signal Transduction DNA Replication DNA repair DNA transcription Mitosis Biology Cell Line Humans Nucleotide Motifs E2F S phase Binding Sites Base Sequence DNA synthesis Cell growth lcsh:R Cancers and Neoplasms DNA Molecular biology E2F Transcription Factors Proliferating cell nuclear antigen biology.protein lcsh:Q Carrier Proteins |
| Zdroj: | PLoS ONE, Vol 8, Iss 4, p e61196 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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