caa a22 4500 606234128 CHVBK 20210128101235.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s11010-014-2244-7 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2244-7 E2F1 regulates p53R2 gene expression in p53-deficient cells [Elektronische Daten] [Jun-Juan Qi, Ling Liu, Ji-Xiang Cao, Guo-Shun An, Shu-Yan Li, Gang Li, Hong-Ti Jia, Ju-Hua Ni] The p53R2 gene encoding a small subunit of the ribonucleotide reductase has been identified as a p53-inducible gene. Although this gene is discovered as a target for p53 family proteins, the mechanism underlying p53R2 induction by DNA damage in p53-defiencient cells remains to be elucidated. In this study, we demonstrate that transcription factor E2F1 regulates the p53R2 gene expression in p53-deficient cells. We found that p53R2 was a target for E2F1 in DNA damage response (DDR), because ectopic expression of E2F1 in HCT116-p53−/− cells resulted in the increase of p53R2 mRNA and protein expression, and silencing E2F1 diminished its basic expression. Combination of luciferase reporter assay with overexpression or knockdown of E2F1 revealed that E2F1 directly activates the p53R2 gene. Chromatin immunoprecipitation (ChIP) assay showed E2F1 directly bound to the site (TTTGGCGG) at position −684 to −677 of the promoter under E2F1 overexpression or adriamycin (ADR) exposure. Moreover, silencing p53R2 could enhance apoptotic cell death in both HCT116-p53−/− and HCT116-p53+/+ compared to ADR exposure, indicating that p53R2 may protect cancer cell from ADR-induced apoptosis. Together, we have identified a new role of E2F1 in the regulation of p53R2 expression in DDR, and silencing p53R2 may sensitize cancer cells to ADR-induced apoptosis. Our data support the notion that p53R2 is a potential target for cancer therapy. The involvement of E2F1-dependent p53R2 activation in DDR will provide further insight into the induction of p53R2 in p53-deficient cells. These data also give us a deeper understanding of E2F1 role in DDR. Springer Science+Business Media New York, 2014 p53R2 nationallicence E2F1 nationallicence ADR-induced DNA damage nationallicence Transcriptional regulation nationallicence Apoptosis nationallicence Qi Jun-Juan Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, 100191, Beijing, People's Republic of China aut Liu Ling Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, 100191, Beijing, People's Republic of China aut Cao Ji-Xiang Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, 100191, Beijing, People's Republic of China aut An Guo-Shun Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, 100191, Beijing, People's Republic of China aut Li Shu-Yan Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, 100191, Beijing, People's Republic of China aut Li Gang Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, 100191, Beijing, People's Republic of China aut Jia Hong-Ti Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, 100191, Beijing, People's Republic of China aut Ni Ju-Hua Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, 100191, Beijing, People's Republic of China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 399/1-2(2015-01-01), 179-188 0300-8177 399:1-2<179 2015 399 11010 https://doi.org/10.1007/s11010-014-2244-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2244-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Qi Jun-Juan Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, 100191, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Liu Ling Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, 100191, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Cao Ji-Xiang Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, 100191, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- An Guo-Shun Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, 100191, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Li Shu-Yan Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, 100191, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Li Gang Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, 100191, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Jia Hong-Ti Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, 100191, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Ni Ju-Hua Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, 100191, Beijing, People's Republic of China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 399/1-2(2015-01-01), 179-188 0300-8177 399:1-2<179 2015 399 11010