The transcription factor p53: not a repressor, solely an activator.
The predominant function of the tumor suppressor p53 is transcriptional regulation. It is generally accepted that p53-dependent transcriptional activation occurs by binding to a specific recognition site in promoters of target genes. Additionally, several models for p53-dependent transcriptional repression have been postulated. Here, we evaluate these models based on a computational meta-analysis of genome-wide data. Surprisingly, several major models of p53-dependent gene regulation are implausible. Meta-analysis of large-scale data is unable to confirm reports on directly repressed p53 target genes and falsifies models of direct repression. This notion is supported by experimental re-analysis of representative genes reported as directly repressed by p53. Therefore, p53 is not a direct repressor of transcription, but solely activates its target genes. Moreover, models based on interference of p53 with activating transcription factors as well as models based on the function of ncRNAs are also not supported by the meta-analysis. As an alternative to models of direct repression, the meta-analysis leads to the conclusion that p53 represses transcription indirectly by activation of the p53-p21-DREAM/RB pathway.
['Fischer|Martin|M|', 'Steiner|Lydia|L|', 'Engeland|Kurt|K|']
D001665:Binding Sites D047369:Chromatin Immunoprecipitation D050759:Cyclin-Dependent Kinase Inhibitor p21 D050684:E2F Transcription Factors D045325:HCT116 Cells D006801:Humans D015201:Meta-Analysis as Topic D011401:Promoter Regions, Genetic D011485:Protein Binding D012333:RNA, Messenger D022661:RNA, Untranslated D060888:Real-Time Polymerase Chain Reaction D012097:Repressor Proteins D016160:Retinoblastoma Protein D015398:Signal Transduction D015533:Transcriptional Activation D016159:Tumor Suppressor Protein p53
p53 CDE, cell cycle-dependent element CDKN1A CHR, cell cycle genes homology region ChIP, chromatin immunoprecipitation DREAM complex DREAM, DP, RB-like, E2F4, and MuvB complex E2F/RB complex HPV, human papilloma virus NF-Y, Nuclear factor Y cdk, cyclin-dependent kinase genome-wide meta-analysis