RBP‐Jκ binds to and represses transcription of the p53 tumor suppressor gene

Cell Biology International - Tập 33 - Trang 318-324 - 2009
Kristy Boggs1, Brystol Henderson1, David Reisman1
1Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA

Tóm tắt

AbstractThe tightly regulated expression of p53 contributes to genomic stability and transcription of the p53 gene is induced prior to cells entering S‐phase, possibly as a mechanism to insure a rapid p53 response in the event of DNA damage. We have previously described the cloning of an additional 1000 bp of upstream p53 sequences that play a role in the regulated expression of p53, and identified that C/EBPβ‐2 participates in inducing p53 gene expression in a cell cycle regulated fashion. This report deals with the transcriptional regulator, RBP‐Jκ, an essential target of the Notch receptor signaling pathway. It binds to the p53 promoter in a cell cycle regulation fashion and also serves to repress p53 gene expression. We conclude from these findings that the coordinate expression of C/EBPβ‐2 and RBP‐Jκ may be linked to p53 transcription during G0 and as cells move into S‐phase. Because defects in the Notch signaling pathway have been implicated in carcinogenesis, aberrant RBP‐Jκ expression and deregulated regulation of the p53 tumor suppressor could be an important step in some forms of cancers.

Tài liệu tham khảo

10.1038/25867 10.1074/jbc.M611675200 10.1038/sj.onc.1209076 10.1016/j.cell.2004.11.022 10.1016/j.ydbio.2006.02.043 10.1007/s000180050268 Freedman D.A., 1999, Regulation of the p53 protein by the MDM2 oncoprotein, Cancer Res, 59, 1 Garkavtsev I., 1998, The candidate tumor suppressor p33ing1 cooperates with p53 in cell growth control, Nature, 391, 295, 10.1038/34675 Ginsberg D., 1990, Protein‐binding elements in the promoter of the mouse p53 gene, Oncogene, 5, 1285 10.1021/bi0271291 10.1073/pnas.91.16.7568 10.1158/0008-5472.CAN-04-3589 10.1073/pnas.96.1.23 10.1126/science.7725102 Hussain S.P., 1998, Molecular epidemiology of human cancer: contribution of mutation spectra studies of tumor suppressor genes, Cancer Res, 58, 4023 10.1038/labinvest.3780266 10.1242/dev.124.20.4133 10.1158/1078-0432.CCR-05-2570 10.1016/0042-6822(81)90327-5 10.1073/pnas.92.10.4407 10.1002/j.1460-2075.1995.tb00123.x 10.1016/S0092-8674(02)01255-2 10.1101/gad.12.11.1621 10.1128/MCB.18.4.2077 10.1128/MCB.25.23.10379-10390.2005 10.1038/nature03147 10.1038/35016125 10.1073/pnas.83.11.3982 10.1038/308199a0 10.1242/dev.01660 10.1016/0092-8674(92)90641-O 10.1101/gad.12.19.2984 Stuart E.T., 1995, Loss of p53 function through PAX‐mediated transcriptional repression, EMBO J, 22, 5638, 10.1002/j.1460-2075.1995.tb00251.x 10.1016/j.cell.2004.06.004 Takaoka A., 2003, Integration of interferon − α/β signaling to p53 responses in tumor suppression and antiviral defense, Nature, 242, 516, 10.1038/nature01850 10.1093/nar/29.6.1373 10.1016/S1044-5323(03)00008-3 10.1073/pnas.96.12.6937 10.1074/jbc.M207363200 10.1016/j.cellbi.2006.11.012 10.1038/nrc864