biostudies-literatureTediose TMedical Research Council2799-812https://www.ebi.ac.uk/biostudies/studies/S-EPMC2875004biostudies-literatureUnknown38(9)Non-malignant cells can be transformed via the activation of kinases that control degradation of neural-restrictive silencer factor (REST). Here, we identify a mechanism that contributes to the activation of genes, expression of which is controlled by responsive elements containing overlapping binding sites for REST and nucleolin. We demonstrate that both phosphorylated and non-phosphorylated nucleolin-bound DNA; however, only phosphorylated nucleolin successfully competed with either full-length REST or a REST-derived DNA-binding peptide, REST68, for binding to the overlapping binding sites. We show that this interplay between the two transcription factors regulates the activation of cell survival and immunomodulatory genes in tumors and non-malignant cells with activated protein kinase CNucleic acids researchInterplay between REST and nucleolin transcription factors: a key mechanism in the overexpression of genes upon increased phosphorylation.PMC2875004G0700102Morgan BPBrennan PTediose TSivasankar BKolev MDonev RfalseInterplay between REST and nucleolin transcription factors: a key mechanism in the overexpression of genes upon increased phosphorylation.Non-malignant cells can be transformed via the activation of kinases that control degradation of neural-restrictive silencer factor (REST). Here, we identify a mechanism that contributes to the activation of genes, expression of which is controlled by responsive elements containing overlapping binding sites for REST and nucleolin. We demonstrate that both phosphorylated and non-phosphorylated nucleolin-bound DNA; however, only phosphorylated nucleolin successfully competed with either full-length REST or a REST-derived DNA-binding peptide, REST68, for binding to the overlapping binding sites. We show that this interplay between the two transcription factors regulates the activation of cell survival and immunomodulatory genes in tumors and non-malignant cells with activated protein kinase C2010-01-01T00:00:00Z2010 May2025-04-26T06:24:06.316Z2019-03-27T00:31:00ZS-EPMC28750042010080310.1093/nar/gkq013