RBP-Jkappa binds to and represses transcription of the p53 tumor suppressor gene.
The 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 1000bp of upstream p53 sequences that play a role in the regulated expression of p53, and identified that C/EBPbeta-2 participates in inducing p53 gene expression in a cell cycle regulated fashion. This report deals with the transcriptional regulator, RBP-Jkappa, 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/EBPbeta-2 and RBP-Jkappa may be linked to p53 transcription during G(0) and as cells move into S-phase. Because defects in the Notch signaling pathway have been implicated in carcinogenesis, aberrant RBP-Jkappa expression and deregulated regulation of the p53 tumor suppressor could be an important step in some forms of cancers.
Boggs
Kristy
K
Department of Biological Sciences, University of South Carolina, Columbia, 29208, USA.
Henderson
Brystol
B
Reisman
David
D
D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D019556:COS Cells; D002453:Cell Cycle; D002460:Cell Line; D002522:Chlorocebus aethiops; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle; D016196:S Phase; D041701:Swiss 3T3 Cells; D014158:Transcription, Genetic; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D022782:CCAAT-Enhancer-Binding Protein-beta; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497571:Rbpj protein, mouse; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53