NDLI: p15PAF Is an Rb/E2F-Regulated S-Phase Protein Essential for DNA Synthesis and Cell Cycle Progression

Content Provider	PubMed Central
Author	Chang, Chih-ning Feng, Mow-jung Chen, Yu-ling Yuan, Ray-hwang Jeng, Yung-ming
Editor	Cimini, Daniela
Copyright Year	2013
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.
Related Links	http://dx.doi.org/10.1371/journal.pone.0061196
Starting Page	61196
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	4
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-04-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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